Obstetrics

Impaired fetal growth does not raise cholesterol levels in adulthood appreciably, according to Rachel Huxley, D.Phil., of the University of Sydney, and her associates.

Proponents of the “fetal origins” hypothesis hold that fetal undernutrition is linked to higher risk of coronary heart disease and related conditions such as high blood pressure, impaired glucose tolerance, and high cholesterol. But it can be argued that there were many methodologic flaws in the collection and interpretation of data supporting this hypothesis. Dr. Huxley and her associates conducted a systematic review of 79 relevant studies involving a total of 74,122 subjects, including 25 studies involving more than 45,000 subjects that were never included in previous examinations of this issue.

They found that for every 1-kg decrease in birth weight, there is only a 2.0-mg/dL rise in cholesterol in later life, which they characterized as a weak link unlikely to affect public health. “Assuming that nutritional intervention in pregnancy could increase birth weight by as much as 100 g, this association would translate into only approximately 0.19 mg/dL lower total cholesterol level,” which would reduce coronary disease risk by less than 0.025%. In contrast, dietary intervention in adulthood can reduce cholesterol level by 15 mg/dL, for a 15% lower CHD risk, they said (JAMA 2004;292:2755–64).

Impaired fetal growth does not raise cholesterol levels in adulthood appreciably, according to Rachel Huxley, D.Phil., of the University of Sydney, and her associates.

Proponents of the “fetal origins” hypothesis hold that fetal undernutrition is linked to higher risk of coronary heart disease and related conditions such as high blood pressure, impaired glucose tolerance, and high cholesterol. But it can be argued that there were many methodologic flaws in the collection and interpretation of data supporting this hypothesis. Dr. Huxley and her associates conducted a systematic review of 79 relevant studies involving a total of 74,122 subjects, including 25 studies involving more than 45,000 subjects that were never included in previous examinations of this issue.

They found that for every 1-kg decrease in birth weight, there is only a 2.0-mg/dL rise in cholesterol in later life, which they characterized as a weak link unlikely to affect public health. “Assuming that nutritional intervention in pregnancy could increase birth weight by as much as 100 g, this association would translate into only approximately 0.19 mg/dL lower total cholesterol level,” which would reduce coronary disease risk by less than 0.025%. In contrast, dietary intervention in adulthood can reduce cholesterol level by 15 mg/dL, for a 15% lower CHD risk, they said (JAMA 2004;292:2755–64).

Impaired fetal growth does not raise cholesterol levels in adulthood appreciably, according to Rachel Huxley, D.Phil., of the University of Sydney, and her associates.

Proponents of the “fetal origins” hypothesis hold that fetal undernutrition is linked to higher risk of coronary heart disease and related conditions such as high blood pressure, impaired glucose tolerance, and high cholesterol. But it can be argued that there were many methodologic flaws in the collection and interpretation of data supporting this hypothesis. Dr. Huxley and her associates conducted a systematic review of 79 relevant studies involving a total of 74,122 subjects, including 25 studies involving more than 45,000 subjects that were never included in previous examinations of this issue.

They found that for every 1-kg decrease in birth weight, there is only a 2.0-mg/dL rise in cholesterol in later life, which they characterized as a weak link unlikely to affect public health. “Assuming that nutritional intervention in pregnancy could increase birth weight by as much as 100 g, this association would translate into only approximately 0.19 mg/dL lower total cholesterol level,” which would reduce coronary disease risk by less than 0.025%. In contrast, dietary intervention in adulthood can reduce cholesterol level by 15 mg/dL, for a 15% lower CHD risk, they said (JAMA 2004;292:2755–64).

A program that sends nurses to visit economically disadvantaged, single mothers during pregnancy and for the child's first 2 years can have long-term benefits, recent data show.

The analysis, which was recently commissioned by the Washington state legislature, shows the largest cost savings of any home visit, child welfare, or early intervention program.

The home visitation program has been developed over 25 years and operates in 21 states and focuses on improving birth outcomes, parenting skills, and children's health and development. It also promotes economic self-sufficiency for families.

Each mother in the Nurse-Family Partnership, develops a long-term relationship with one nurse who follows detailed guidelines and is trained in prenatal care and early child development.

The latest data, published in two articles in the journal Pediatrics, are from controlled, randomized trials conducted in two settings: among low-income African American mothers in Memphis, and among an ethnically and racially diverse group of low-income Denver women.

The women and children in Memphis were interviewed and evaluated 4 years after the program ended, near the child's sixth birthday. Those in Denver were evaluated 2 years after the program ended.

“The effects of the program … increase the likelihood that nurse-visited children will adjust more effectively as they proceed through elementary school,” reported David L. Olds, Ph.D., of the department of pediatrics at the University of Colorado Health Sciences Center in Denver, and his associates (Pediatrics 2004;114:1550–9).

Of the 743 women in Memphis who were randomized to the nurse home visitation program or one of three other intervention groups, those enrolled in the nurse visitation program had fewer subsequent pregnancies and births (1 vs. 1.3 births), and longer intervals between births of their first and second children (34 vs. 30 months).

They also had longer relationships with their partners, used welfare and food stamps for fewer months, and were more likely to enroll their children in some form of preschool or licensed day care.

The children of these nurse-visited women had higher scores on tests of intellectual functioning and receptive language, and fewer behavioral problems in the borderline or clinical range (2% vs. 5%, based on the Achenbach Child Behavior Checklist).

Among children born to women with low psychological resources (limited intellectual functioning, mental health, and sense of control), those whose mothers met with the nurses had higher arithmetic achievement test scores and expressed less dysregulated aggression and incoherence when asked to respond to and finish story beginnings, the investigators said.

The program “is so effective [because] they've tested [and shown] the importance of using nurses instead of social workers,” said Steve Aos, associate director of the Washington State Institute for Public Policy, a nonpartisan organization that produced the analysis that is now gaining focus in Washington state.

“And especially since the program has gone national, Dr. Olds makes sure the program is done by the book. … [He appears to have] hit on a better theoretical model for intervention,” Mr. Aos said.

Dr. Olds, who developed and has refined the program over the years, said he hopes to examine more the extent to which the program produces comparable effects across different populations. Some effects—such as reductions in prenatal tobacco use and reductions in the rates and intervals of subsequent pregnancies-—seem to be fairly consistent. Other effects vary among populations.

The first trial of the program, which began about 20 years ago, involved low-income white families in rural New York. Researchers found less alcohol use and better behavior among teenage children of nurse-visited mothers has been published, and the families are still being followed.

The evaluation done by Mr. Aos' organization at the request of the Washington state legislature showed that the Nurse-Family Partnership costs about $9,000 per family and had a record net benefit of more than $17,000 per youth, in terms of welfare, criminal justice system, medical, and other cost savings.

Most of the 160 Nurse-Family Partnership programs across the country are administered through county health programs. In the long term, however, “things will have to change—there just aren't enough funding streams,” said Matt Buhr-Vogel, manager of site development for the new Nurse-Family Partnership national office in Denver.

A program that sends nurses to visit economically disadvantaged, single mothers during pregnancy and for the child's first 2 years can have long-term benefits, recent data show.

The analysis, which was recently commissioned by the Washington state legislature, shows the largest cost savings of any home visit, child welfare, or early intervention program.

The home visitation program has been developed over 25 years and operates in 21 states and focuses on improving birth outcomes, parenting skills, and children's health and development. It also promotes economic self-sufficiency for families.

Each mother in the Nurse-Family Partnership, develops a long-term relationship with one nurse who follows detailed guidelines and is trained in prenatal care and early child development.

The latest data, published in two articles in the journal Pediatrics, are from controlled, randomized trials conducted in two settings: among low-income African American mothers in Memphis, and among an ethnically and racially diverse group of low-income Denver women.

The women and children in Memphis were interviewed and evaluated 4 years after the program ended, near the child's sixth birthday. Those in Denver were evaluated 2 years after the program ended.

“The effects of the program … increase the likelihood that nurse-visited children will adjust more effectively as they proceed through elementary school,” reported David L. Olds, Ph.D., of the department of pediatrics at the University of Colorado Health Sciences Center in Denver, and his associates (Pediatrics 2004;114:1550–9).

Of the 743 women in Memphis who were randomized to the nurse home visitation program or one of three other intervention groups, those enrolled in the nurse visitation program had fewer subsequent pregnancies and births (1 vs. 1.3 births), and longer intervals between births of their first and second children (34 vs. 30 months).

They also had longer relationships with their partners, used welfare and food stamps for fewer months, and were more likely to enroll their children in some form of preschool or licensed day care.

The children of these nurse-visited women had higher scores on tests of intellectual functioning and receptive language, and fewer behavioral problems in the borderline or clinical range (2% vs. 5%, based on the Achenbach Child Behavior Checklist).

Among children born to women with low psychological resources (limited intellectual functioning, mental health, and sense of control), those whose mothers met with the nurses had higher arithmetic achievement test scores and expressed less dysregulated aggression and incoherence when asked to respond to and finish story beginnings, the investigators said.

The program “is so effective [because] they've tested [and shown] the importance of using nurses instead of social workers,” said Steve Aos, associate director of the Washington State Institute for Public Policy, a nonpartisan organization that produced the analysis that is now gaining focus in Washington state.

“And especially since the program has gone national, Dr. Olds makes sure the program is done by the book. … [He appears to have] hit on a better theoretical model for intervention,” Mr. Aos said.

Dr. Olds, who developed and has refined the program over the years, said he hopes to examine more the extent to which the program produces comparable effects across different populations. Some effects—such as reductions in prenatal tobacco use and reductions in the rates and intervals of subsequent pregnancies-—seem to be fairly consistent. Other effects vary among populations.

The first trial of the program, which began about 20 years ago, involved low-income white families in rural New York. Researchers found less alcohol use and better behavior among teenage children of nurse-visited mothers has been published, and the families are still being followed.

The evaluation done by Mr. Aos' organization at the request of the Washington state legislature showed that the Nurse-Family Partnership costs about $9,000 per family and had a record net benefit of more than $17,000 per youth, in terms of welfare, criminal justice system, medical, and other cost savings.

Most of the 160 Nurse-Family Partnership programs across the country are administered through county health programs. In the long term, however, “things will have to change—there just aren't enough funding streams,” said Matt Buhr-Vogel, manager of site development for the new Nurse-Family Partnership national office in Denver.

A program that sends nurses to visit economically disadvantaged, single mothers during pregnancy and for the child's first 2 years can have long-term benefits, recent data show.

The analysis, which was recently commissioned by the Washington state legislature, shows the largest cost savings of any home visit, child welfare, or early intervention program.

The home visitation program has been developed over 25 years and operates in 21 states and focuses on improving birth outcomes, parenting skills, and children's health and development. It also promotes economic self-sufficiency for families.

Each mother in the Nurse-Family Partnership, develops a long-term relationship with one nurse who follows detailed guidelines and is trained in prenatal care and early child development.

The latest data, published in two articles in the journal Pediatrics, are from controlled, randomized trials conducted in two settings: among low-income African American mothers in Memphis, and among an ethnically and racially diverse group of low-income Denver women.

The women and children in Memphis were interviewed and evaluated 4 years after the program ended, near the child's sixth birthday. Those in Denver were evaluated 2 years after the program ended.

“The effects of the program … increase the likelihood that nurse-visited children will adjust more effectively as they proceed through elementary school,” reported David L. Olds, Ph.D., of the department of pediatrics at the University of Colorado Health Sciences Center in Denver, and his associates (Pediatrics 2004;114:1550–9).

Of the 743 women in Memphis who were randomized to the nurse home visitation program or one of three other intervention groups, those enrolled in the nurse visitation program had fewer subsequent pregnancies and births (1 vs. 1.3 births), and longer intervals between births of their first and second children (34 vs. 30 months).

They also had longer relationships with their partners, used welfare and food stamps for fewer months, and were more likely to enroll their children in some form of preschool or licensed day care.

The children of these nurse-visited women had higher scores on tests of intellectual functioning and receptive language, and fewer behavioral problems in the borderline or clinical range (2% vs. 5%, based on the Achenbach Child Behavior Checklist).

Among children born to women with low psychological resources (limited intellectual functioning, mental health, and sense of control), those whose mothers met with the nurses had higher arithmetic achievement test scores and expressed less dysregulated aggression and incoherence when asked to respond to and finish story beginnings, the investigators said.

The program “is so effective [because] they've tested [and shown] the importance of using nurses instead of social workers,” said Steve Aos, associate director of the Washington State Institute for Public Policy, a nonpartisan organization that produced the analysis that is now gaining focus in Washington state.

“And especially since the program has gone national, Dr. Olds makes sure the program is done by the book. … [He appears to have] hit on a better theoretical model for intervention,” Mr. Aos said.

Dr. Olds, who developed and has refined the program over the years, said he hopes to examine more the extent to which the program produces comparable effects across different populations. Some effects—such as reductions in prenatal tobacco use and reductions in the rates and intervals of subsequent pregnancies-—seem to be fairly consistent. Other effects vary among populations.

The first trial of the program, which began about 20 years ago, involved low-income white families in rural New York. Researchers found less alcohol use and better behavior among teenage children of nurse-visited mothers has been published, and the families are still being followed.

The evaluation done by Mr. Aos' organization at the request of the Washington state legislature showed that the Nurse-Family Partnership costs about $9,000 per family and had a record net benefit of more than $17,000 per youth, in terms of welfare, criminal justice system, medical, and other cost savings.

Most of the 160 Nurse-Family Partnership programs across the country are administered through county health programs. In the long term, however, “things will have to change—there just aren't enough funding streams,” said Matt Buhr-Vogel, manager of site development for the new Nurse-Family Partnership national office in Denver.

SAN FRANCISCO — Use of forceps or vacuum extractor during a vaginal delivery seldom is the sole cause of litigation, but you can reduce that risk even more, several speakers said at a conference on ob.gyn., perinatal medicine, neonatology, and the law.

Operative vaginal delivery can invite litigation when one of the following happens, according to Larry C. Gilstrap III, M.D., professor and chair of ob.gyn. and reproductive services at the University of Texas at Houston:

▸ Forceps or vacuum are used for an inappropriate indication, and the baby is damaged. Indications include a prolonged second stage of labor, fetal compromise, or a need to shorten the second stage for maternal health reasons. A prolonged second stage for nulliparous women is defined as 2 hours of labor, or 3 hours with regional anesthesia. In multiparous women, a prolonged second stage is 1 hour of labor, or 2 hours with regional anesthesia.

▸ Forceps or vacuum are used for convenience. Labor and delivery are going well, but the physician grabs the forceps or vacuum to speed things along to get to a party or a tee time. “That sounds kind of ridiculous, but I've been asked to look at [such] cases. You can't defend that case,” he said at the meeting, sponsored by Boston University and the Center for Human Genetics.

▸ The mother doesn't know what to expect. Inform her of the indications, the procedure, and what to expect, Dr. Gilstrap said. “The residents and nurses are amazed sometimes at how much time I take when I go up to the head of the table and I explain to the patient why I'm going to use forceps, for example.”

He shows the mother the instrument and describes how it is going to fit on the baby's cheek, not the top of the head. He explains that the forceps will make an indentation on the cheeks that may be coded as trauma by the pediatrician and emphasizes that it is not trauma and will go away.

“I explain to them that several of my daughters and several grandchildren were delivered by forceps,” he added.

“I think this is a problem of public perception,” agreed Dennis J. Sinclitico, J.D., in a commentary on Dr. Gilstrap's presentation. Many childbirth classes don't mention operative vaginal deliveries. Trying to educate the woman and obtain informed consent in the midst of a delivery is not an ideal situation. It is better to give the patient information about the potential for operative vaginal delivery before labor starts, said Mr. Sinclitico, who is a defense attorney in Long Beach, Calif.

▸ An inexperienced operator wields the forceps or vacuum. It is okay to have a resident perform the operative vaginal delivery as long as an experienced teacher is present, Dr. Gilstrap said.

With trends toward increased numbers of cesarean sections and fewer forceps deliveries over the last 2 decades, skill levels with forceps are dropping, Mr. Sinclitico added.

▸ Forceps or the vacuum are applied incorrectly. Forceps should be placed halfway between the eyes and ears and down on the face, not the skull, Dr. Gilstrap said. Position the center of a vacuum cup 3 cm from the posterior fontanel, which puts the leading part of the cup about 3 cm from the anterior fontanel.

▸ Precautions are inadequate. If the fetus has “considerable evidence of nonreassuring heart tones,” it may be appropriate to attempt forceps or vacuum delivery, but start setting up for a C-section at the same time, James S. Bostwick, J.D., advised in a separate commentary. Or move the patient to the operating room before trying the forceps or vacuum, said Mr. Bostwick, a plaintiff's attorney in San Francisco, Calif.

▸ There is inadequate documentation. A lack of a written description of what happened, and when, leads to reliance on potentially conflicting oral accounts by physicians, nurses, and the baby's parents.

Be sure to document why you acted as you did, Mr. Sinclitico stressed. “These cases are easier to defend when my client has done something and has exercised his or her clinical judgment” rather than standing by or waiting for something to happen, he said.

SAN FRANCISCO — Use of forceps or vacuum extractor during a vaginal delivery seldom is the sole cause of litigation, but you can reduce that risk even more, several speakers said at a conference on ob.gyn., perinatal medicine, neonatology, and the law.

Operative vaginal delivery can invite litigation when one of the following happens, according to Larry C. Gilstrap III, M.D., professor and chair of ob.gyn. and reproductive services at the University of Texas at Houston:

▸ Forceps or vacuum are used for an inappropriate indication, and the baby is damaged. Indications include a prolonged second stage of labor, fetal compromise, or a need to shorten the second stage for maternal health reasons. A prolonged second stage for nulliparous women is defined as 2 hours of labor, or 3 hours with regional anesthesia. In multiparous women, a prolonged second stage is 1 hour of labor, or 2 hours with regional anesthesia.

▸ Forceps or vacuum are used for convenience. Labor and delivery are going well, but the physician grabs the forceps or vacuum to speed things along to get to a party or a tee time. “That sounds kind of ridiculous, but I've been asked to look at [such] cases. You can't defend that case,” he said at the meeting, sponsored by Boston University and the Center for Human Genetics.

▸ The mother doesn't know what to expect. Inform her of the indications, the procedure, and what to expect, Dr. Gilstrap said. “The residents and nurses are amazed sometimes at how much time I take when I go up to the head of the table and I explain to the patient why I'm going to use forceps, for example.”

He shows the mother the instrument and describes how it is going to fit on the baby's cheek, not the top of the head. He explains that the forceps will make an indentation on the cheeks that may be coded as trauma by the pediatrician and emphasizes that it is not trauma and will go away.

“I explain to them that several of my daughters and several grandchildren were delivered by forceps,” he added.

“I think this is a problem of public perception,” agreed Dennis J. Sinclitico, J.D., in a commentary on Dr. Gilstrap's presentation. Many childbirth classes don't mention operative vaginal deliveries. Trying to educate the woman and obtain informed consent in the midst of a delivery is not an ideal situation. It is better to give the patient information about the potential for operative vaginal delivery before labor starts, said Mr. Sinclitico, who is a defense attorney in Long Beach, Calif.

▸ An inexperienced operator wields the forceps or vacuum. It is okay to have a resident perform the operative vaginal delivery as long as an experienced teacher is present, Dr. Gilstrap said.

With trends toward increased numbers of cesarean sections and fewer forceps deliveries over the last 2 decades, skill levels with forceps are dropping, Mr. Sinclitico added.

▸ Forceps or the vacuum are applied incorrectly. Forceps should be placed halfway between the eyes and ears and down on the face, not the skull, Dr. Gilstrap said. Position the center of a vacuum cup 3 cm from the posterior fontanel, which puts the leading part of the cup about 3 cm from the anterior fontanel.

▸ Precautions are inadequate. If the fetus has “considerable evidence of nonreassuring heart tones,” it may be appropriate to attempt forceps or vacuum delivery, but start setting up for a C-section at the same time, James S. Bostwick, J.D., advised in a separate commentary. Or move the patient to the operating room before trying the forceps or vacuum, said Mr. Bostwick, a plaintiff's attorney in San Francisco, Calif.

▸ There is inadequate documentation. A lack of a written description of what happened, and when, leads to reliance on potentially conflicting oral accounts by physicians, nurses, and the baby's parents.

Be sure to document why you acted as you did, Mr. Sinclitico stressed. “These cases are easier to defend when my client has done something and has exercised his or her clinical judgment” rather than standing by or waiting for something to happen, he said.

SAN FRANCISCO — Use of forceps or vacuum extractor during a vaginal delivery seldom is the sole cause of litigation, but you can reduce that risk even more, several speakers said at a conference on ob.gyn., perinatal medicine, neonatology, and the law.

Operative vaginal delivery can invite litigation when one of the following happens, according to Larry C. Gilstrap III, M.D., professor and chair of ob.gyn. and reproductive services at the University of Texas at Houston:

▸ Forceps or vacuum are used for an inappropriate indication, and the baby is damaged. Indications include a prolonged second stage of labor, fetal compromise, or a need to shorten the second stage for maternal health reasons. A prolonged second stage for nulliparous women is defined as 2 hours of labor, or 3 hours with regional anesthesia. In multiparous women, a prolonged second stage is 1 hour of labor, or 2 hours with regional anesthesia.

▸ Forceps or vacuum are used for convenience. Labor and delivery are going well, but the physician grabs the forceps or vacuum to speed things along to get to a party or a tee time. “That sounds kind of ridiculous, but I've been asked to look at [such] cases. You can't defend that case,” he said at the meeting, sponsored by Boston University and the Center for Human Genetics.

▸ The mother doesn't know what to expect. Inform her of the indications, the procedure, and what to expect, Dr. Gilstrap said. “The residents and nurses are amazed sometimes at how much time I take when I go up to the head of the table and I explain to the patient why I'm going to use forceps, for example.”

He shows the mother the instrument and describes how it is going to fit on the baby's cheek, not the top of the head. He explains that the forceps will make an indentation on the cheeks that may be coded as trauma by the pediatrician and emphasizes that it is not trauma and will go away.

“I explain to them that several of my daughters and several grandchildren were delivered by forceps,” he added.

“I think this is a problem of public perception,” agreed Dennis J. Sinclitico, J.D., in a commentary on Dr. Gilstrap's presentation. Many childbirth classes don't mention operative vaginal deliveries. Trying to educate the woman and obtain informed consent in the midst of a delivery is not an ideal situation. It is better to give the patient information about the potential for operative vaginal delivery before labor starts, said Mr. Sinclitico, who is a defense attorney in Long Beach, Calif.

▸ An inexperienced operator wields the forceps or vacuum. It is okay to have a resident perform the operative vaginal delivery as long as an experienced teacher is present, Dr. Gilstrap said.

With trends toward increased numbers of cesarean sections and fewer forceps deliveries over the last 2 decades, skill levels with forceps are dropping, Mr. Sinclitico added.

▸ Forceps or the vacuum are applied incorrectly. Forceps should be placed halfway between the eyes and ears and down on the face, not the skull, Dr. Gilstrap said. Position the center of a vacuum cup 3 cm from the posterior fontanel, which puts the leading part of the cup about 3 cm from the anterior fontanel.

▸ Precautions are inadequate. If the fetus has “considerable evidence of nonreassuring heart tones,” it may be appropriate to attempt forceps or vacuum delivery, but start setting up for a C-section at the same time, James S. Bostwick, J.D., advised in a separate commentary. Or move the patient to the operating room before trying the forceps or vacuum, said Mr. Bostwick, a plaintiff's attorney in San Francisco, Calif.

▸ There is inadequate documentation. A lack of a written description of what happened, and when, leads to reliance on potentially conflicting oral accounts by physicians, nurses, and the baby's parents.

Be sure to document why you acted as you did, Mr. Sinclitico stressed. “These cases are easier to defend when my client has done something and has exercised his or her clinical judgment” rather than standing by or waiting for something to happen, he said.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of this agent in pregnancy, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus. Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy.

In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

The drug also was not linked to any unusual side effects in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children. “I think we can ensure that at such a low level there is no risk,” Dr. Piette said.

Some reports have noted teratogenicity with high-dose chloroquine; one case occurred in a pregnant woman with lupus. These have included a few cases of ear or eye toxicity. Dr. Piette said that he recommends contraception in patients who receive chloroquine.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of this agent in pregnancy, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus. Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy.

In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

The drug also was not linked to any unusual side effects in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children. “I think we can ensure that at such a low level there is no risk,” Dr. Piette said.

Some reports have noted teratogenicity with high-dose chloroquine; one case occurred in a pregnant woman with lupus. These have included a few cases of ear or eye toxicity. Dr. Piette said that he recommends contraception in patients who receive chloroquine.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of this agent in pregnancy, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus. Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy.

In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

The drug also was not linked to any unusual side effects in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children. “I think we can ensure that at such a low level there is no risk,” Dr. Piette said.

Some reports have noted teratogenicity with high-dose chloroquine; one case occurred in a pregnant woman with lupus. These have included a few cases of ear or eye toxicity. Dr. Piette said that he recommends contraception in patients who receive chloroquine.

VIENNA — Decreased urinary placental growth factor at midgestation is strongly associated with the subsequent development of early-onset preeclampsia, S. Ananth Karumanchi, M.D., reported.

“Low urinary PlGF antedates the clinical diagnosis of preeclampsia and may serve as a screening test to predict who will develop early-onset disease,” Dr. Karumanchi said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

The findings, published soon after the congress, come from a nested case-control study within the Calcium for Preeclampsia Prevention trial of healthy nulliparous women enrolled at five U.S. university medical centers during 1992–1995. Frozen serum and urine samples from 120 women with preeclampsia were compared with those of 120 matched normotensive controls (JAMA 2005;293:77–85).

In all the women, urinary PlGF levels increased during the first two trimesters, with a more rapid increase after 21–24 weeks and a peak at 29–33 weeks. However, those levels were significantly lower among the women who subsequently developed preeclampsia at weeks 25–28, 29–32, and 33–36. Differences were particularly large between the controls and the women who subsequently developed preeclampsia before 37 weeks or who had preeclampsia with a small-for-gestational age (SGA) infant.

Alterations in urinary PlGF levels at 21–32 weeks were also more pronounced in women who subsequently developed preeclampsia before 37 weeks (87 pg/mL) than among those who had onset of preeclampsia at term (223 pg/mL).

At 33–42 weeks, those levels were 22 vs. 118 pg/mL, lead author Richard J. Levine, M.D., of the National Institute of Child Health and Human Development, Bethesda, Md., and his associates reported in the published article.

The women were divided by quartiles of urinary PlGF obtained at 21–32 weeks' gestation and the results adjusted for gestational age at specimen collection, storage time, body mass index, and maternal age.

Compared with women in the upper three quartiles, the odds ratio was 22.5 for later development of preterm preeclampsia among the women with PlGF concentrations in the lowest quartile (less than 118 pg/mL). The association was even stronger when restricted to just morning urine specimens, with an odds ratio of 39.5.

For term preeclampsia, the adjusted odds ratios of lowest vs. the upper three quartiles of PlGF concentration were 2.2 at 21–32 weeks and 2.3 at 33–42 weeks' gestation. The data also suggested a strong association between low urinary PlGF and a substantially increased risk for preeclampsia with an SGA infant, but the numbers were too small to make a stable estimate, Dr. Levine and his associates noted.

Adjusting the results for urinary creatinine concentration did not change the strength of the associations, they said.

Previous data from this research group showed that increased circulating serum levels of the angiogenic factor soluble fms-like tyrosine kinase (sFlt-1) were predictive of subsequent preeclampsia (N. Engl. J. Med. 2004;350:672–83).

But because the sFlt-1 molecule is too large to be filtered into urine, the current study focused on PlGF, which binds to sFlt-1, as a more clinically feasible alternative. If a reliable dipstick assay could be developed for urine screening of all pregnant women for urine PlGF, then subsequent serum measurements of both PlGF and sFlt-1 could minimize false-positive results from urine testing, the researchers said.

At the congress, Dr. Karumanchi, a nephrologist at Beth Israel Deaconess Medical Center, Boston, said, “Obviously, this is a retrospective study done using specimens frozen for several years, and we don't know if it can be reproduced prospectively. Nevertheless, it does prove the hypothesis that angiogenic factors play a critical role in the pathogenesis of this syndrome.”

VIENNA — Decreased urinary placental growth factor at midgestation is strongly associated with the subsequent development of early-onset preeclampsia, S. Ananth Karumanchi, M.D., reported.

“Low urinary PlGF antedates the clinical diagnosis of preeclampsia and may serve as a screening test to predict who will develop early-onset disease,” Dr. Karumanchi said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

The findings, published soon after the congress, come from a nested case-control study within the Calcium for Preeclampsia Prevention trial of healthy nulliparous women enrolled at five U.S. university medical centers during 1992–1995. Frozen serum and urine samples from 120 women with preeclampsia were compared with those of 120 matched normotensive controls (JAMA 2005;293:77–85).

In all the women, urinary PlGF levels increased during the first two trimesters, with a more rapid increase after 21–24 weeks and a peak at 29–33 weeks. However, those levels were significantly lower among the women who subsequently developed preeclampsia at weeks 25–28, 29–32, and 33–36. Differences were particularly large between the controls and the women who subsequently developed preeclampsia before 37 weeks or who had preeclampsia with a small-for-gestational age (SGA) infant.

Alterations in urinary PlGF levels at 21–32 weeks were also more pronounced in women who subsequently developed preeclampsia before 37 weeks (87 pg/mL) than among those who had onset of preeclampsia at term (223 pg/mL).

At 33–42 weeks, those levels were 22 vs. 118 pg/mL, lead author Richard J. Levine, M.D., of the National Institute of Child Health and Human Development, Bethesda, Md., and his associates reported in the published article.

The women were divided by quartiles of urinary PlGF obtained at 21–32 weeks' gestation and the results adjusted for gestational age at specimen collection, storage time, body mass index, and maternal age.

Compared with women in the upper three quartiles, the odds ratio was 22.5 for later development of preterm preeclampsia among the women with PlGF concentrations in the lowest quartile (less than 118 pg/mL). The association was even stronger when restricted to just morning urine specimens, with an odds ratio of 39.5.

For term preeclampsia, the adjusted odds ratios of lowest vs. the upper three quartiles of PlGF concentration were 2.2 at 21–32 weeks and 2.3 at 33–42 weeks' gestation. The data also suggested a strong association between low urinary PlGF and a substantially increased risk for preeclampsia with an SGA infant, but the numbers were too small to make a stable estimate, Dr. Levine and his associates noted.

Adjusting the results for urinary creatinine concentration did not change the strength of the associations, they said.

Previous data from this research group showed that increased circulating serum levels of the angiogenic factor soluble fms-like tyrosine kinase (sFlt-1) were predictive of subsequent preeclampsia (N. Engl. J. Med. 2004;350:672–83).

But because the sFlt-1 molecule is too large to be filtered into urine, the current study focused on PlGF, which binds to sFlt-1, as a more clinically feasible alternative. If a reliable dipstick assay could be developed for urine screening of all pregnant women for urine PlGF, then subsequent serum measurements of both PlGF and sFlt-1 could minimize false-positive results from urine testing, the researchers said.

At the congress, Dr. Karumanchi, a nephrologist at Beth Israel Deaconess Medical Center, Boston, said, “Obviously, this is a retrospective study done using specimens frozen for several years, and we don't know if it can be reproduced prospectively. Nevertheless, it does prove the hypothesis that angiogenic factors play a critical role in the pathogenesis of this syndrome.”

VIENNA — Decreased urinary placental growth factor at midgestation is strongly associated with the subsequent development of early-onset preeclampsia, S. Ananth Karumanchi, M.D., reported.

“Low urinary PlGF antedates the clinical diagnosis of preeclampsia and may serve as a screening test to predict who will develop early-onset disease,” Dr. Karumanchi said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

The findings, published soon after the congress, come from a nested case-control study within the Calcium for Preeclampsia Prevention trial of healthy nulliparous women enrolled at five U.S. university medical centers during 1992–1995. Frozen serum and urine samples from 120 women with preeclampsia were compared with those of 120 matched normotensive controls (JAMA 2005;293:77–85).

In all the women, urinary PlGF levels increased during the first two trimesters, with a more rapid increase after 21–24 weeks and a peak at 29–33 weeks. However, those levels were significantly lower among the women who subsequently developed preeclampsia at weeks 25–28, 29–32, and 33–36. Differences were particularly large between the controls and the women who subsequently developed preeclampsia before 37 weeks or who had preeclampsia with a small-for-gestational age (SGA) infant.

Alterations in urinary PlGF levels at 21–32 weeks were also more pronounced in women who subsequently developed preeclampsia before 37 weeks (87 pg/mL) than among those who had onset of preeclampsia at term (223 pg/mL).

At 33–42 weeks, those levels were 22 vs. 118 pg/mL, lead author Richard J. Levine, M.D., of the National Institute of Child Health and Human Development, Bethesda, Md., and his associates reported in the published article.

The women were divided by quartiles of urinary PlGF obtained at 21–32 weeks' gestation and the results adjusted for gestational age at specimen collection, storage time, body mass index, and maternal age.

Compared with women in the upper three quartiles, the odds ratio was 22.5 for later development of preterm preeclampsia among the women with PlGF concentrations in the lowest quartile (less than 118 pg/mL). The association was even stronger when restricted to just morning urine specimens, with an odds ratio of 39.5.

For term preeclampsia, the adjusted odds ratios of lowest vs. the upper three quartiles of PlGF concentration were 2.2 at 21–32 weeks and 2.3 at 33–42 weeks' gestation. The data also suggested a strong association between low urinary PlGF and a substantially increased risk for preeclampsia with an SGA infant, but the numbers were too small to make a stable estimate, Dr. Levine and his associates noted.

Adjusting the results for urinary creatinine concentration did not change the strength of the associations, they said.

Previous data from this research group showed that increased circulating serum levels of the angiogenic factor soluble fms-like tyrosine kinase (sFlt-1) were predictive of subsequent preeclampsia (N. Engl. J. Med. 2004;350:672–83).

But because the sFlt-1 molecule is too large to be filtered into urine, the current study focused on PlGF, which binds to sFlt-1, as a more clinically feasible alternative. If a reliable dipstick assay could be developed for urine screening of all pregnant women for urine PlGF, then subsequent serum measurements of both PlGF and sFlt-1 could minimize false-positive results from urine testing, the researchers said.

At the congress, Dr. Karumanchi, a nephrologist at Beth Israel Deaconess Medical Center, Boston, said, “Obviously, this is a retrospective study done using specimens frozen for several years, and we don't know if it can be reproduced prospectively. Nevertheless, it does prove the hypothesis that angiogenic factors play a critical role in the pathogenesis of this syndrome.”

SAN FRANCISCO — Before you write an order for Pitocin administration to induce or augment labor, be sure you know your hospital's protocol for Pitocin use, Dennis J. Sinclitico, J.D., advised.

In the three most recent obstetrical malpractice cases in which he served as a defense attorney, the physicians gave nurses orders for Pitocin (oxytocin) that contradicted the hospital protocol for Pitocin use, he said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

That contradiction forces nurses to make decisions about the utilization, titration, and discontinuation of Pitocin “without the comfort and background of their own protocol,” he noted. Often there is no further physician involvement besides orders to “call me when you're ready” for delivery.

Basically abandoning nurses with contradictory orders is “a terrible mistake and indefensible in many instances,” said Mr. Sinclitico, a defense lawyer in Long Beach, Calif.

If you want to leave orders for Pitocin use that differ from the hospital's protocol, document why you think your approach to management is important and appropriate. Give the nurses written instructions documenting that your orders differ from the protocol and tell them how and when to adjust, titrate, or discontinue the Pitocin dosage. Provide written instructions on how and when the nurses should contact you.

Pitocin is a player in virtually every case he defends, even if it's not a relevant factor, Mr. Sinclitico noted. “I can't remember a case recently in which Pitocin wasn't ordered in some fashion,” he said at the meeting, sponsored by Boston University and the Center for Human Genetics.

The biggest problem he sees in the cases he defends that involve Pitocin administration stem from insufficient response to findings on the fetal heart rate monitoring strip. Fifteen, 20, or 60 minutes go by before nurses or physicians respond to a potential problem identified by the strip, and the health care workers leave insufficient documentation about the course of events, their timing, and reasons for acting or not acting.

“If I have a practice tip for you, it would be to go back to your hospital and emphasize the notion that if you're going to allow nurses to make those judgments, they should be made appropriately and in a timely fashion,” he said.

Because individual responses to Pitocin differ, the dose must be monitored carefully and adjusted as needed. Used properly, Pitocin can prevent the need for cesarean section in some deliveries. Risks from the force of contractions induced by Pitocin include potentially greater reductions in uterine blood flow than occur with natural contractions, which can lead to a greater reduction in oxygen for the fetus and possible fetal distress.

SAN FRANCISCO — Before you write an order for Pitocin administration to induce or augment labor, be sure you know your hospital's protocol for Pitocin use, Dennis J. Sinclitico, J.D., advised.

In the three most recent obstetrical malpractice cases in which he served as a defense attorney, the physicians gave nurses orders for Pitocin (oxytocin) that contradicted the hospital protocol for Pitocin use, he said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

That contradiction forces nurses to make decisions about the utilization, titration, and discontinuation of Pitocin “without the comfort and background of their own protocol,” he noted. Often there is no further physician involvement besides orders to “call me when you're ready” for delivery.

Basically abandoning nurses with contradictory orders is “a terrible mistake and indefensible in many instances,” said Mr. Sinclitico, a defense lawyer in Long Beach, Calif.

If you want to leave orders for Pitocin use that differ from the hospital's protocol, document why you think your approach to management is important and appropriate. Give the nurses written instructions documenting that your orders differ from the protocol and tell them how and when to adjust, titrate, or discontinue the Pitocin dosage. Provide written instructions on how and when the nurses should contact you.

Pitocin is a player in virtually every case he defends, even if it's not a relevant factor, Mr. Sinclitico noted. “I can't remember a case recently in which Pitocin wasn't ordered in some fashion,” he said at the meeting, sponsored by Boston University and the Center for Human Genetics.

The biggest problem he sees in the cases he defends that involve Pitocin administration stem from insufficient response to findings on the fetal heart rate monitoring strip. Fifteen, 20, or 60 minutes go by before nurses or physicians respond to a potential problem identified by the strip, and the health care workers leave insufficient documentation about the course of events, their timing, and reasons for acting or not acting.

“If I have a practice tip for you, it would be to go back to your hospital and emphasize the notion that if you're going to allow nurses to make those judgments, they should be made appropriately and in a timely fashion,” he said.

Because individual responses to Pitocin differ, the dose must be monitored carefully and adjusted as needed. Used properly, Pitocin can prevent the need for cesarean section in some deliveries. Risks from the force of contractions induced by Pitocin include potentially greater reductions in uterine blood flow than occur with natural contractions, which can lead to a greater reduction in oxygen for the fetus and possible fetal distress.

SAN FRANCISCO — Before you write an order for Pitocin administration to induce or augment labor, be sure you know your hospital's protocol for Pitocin use, Dennis J. Sinclitico, J.D., advised.

In the three most recent obstetrical malpractice cases in which he served as a defense attorney, the physicians gave nurses orders for Pitocin (oxytocin) that contradicted the hospital protocol for Pitocin use, he said at a conference on obstetrics, gynecology, perinatal medicine, neonatology, and the law.

That contradiction forces nurses to make decisions about the utilization, titration, and discontinuation of Pitocin “without the comfort and background of their own protocol,” he noted. Often there is no further physician involvement besides orders to “call me when you're ready” for delivery.

Basically abandoning nurses with contradictory orders is “a terrible mistake and indefensible in many instances,” said Mr. Sinclitico, a defense lawyer in Long Beach, Calif.

If you want to leave orders for Pitocin use that differ from the hospital's protocol, document why you think your approach to management is important and appropriate. Give the nurses written instructions documenting that your orders differ from the protocol and tell them how and when to adjust, titrate, or discontinue the Pitocin dosage. Provide written instructions on how and when the nurses should contact you.

Pitocin is a player in virtually every case he defends, even if it's not a relevant factor, Mr. Sinclitico noted. “I can't remember a case recently in which Pitocin wasn't ordered in some fashion,” he said at the meeting, sponsored by Boston University and the Center for Human Genetics.

The biggest problem he sees in the cases he defends that involve Pitocin administration stem from insufficient response to findings on the fetal heart rate monitoring strip. Fifteen, 20, or 60 minutes go by before nurses or physicians respond to a potential problem identified by the strip, and the health care workers leave insufficient documentation about the course of events, their timing, and reasons for acting or not acting.

“If I have a practice tip for you, it would be to go back to your hospital and emphasize the notion that if you're going to allow nurses to make those judgments, they should be made appropriately and in a timely fashion,” he said.

Because individual responses to Pitocin differ, the dose must be monitored carefully and adjusted as needed. Used properly, Pitocin can prevent the need for cesarean section in some deliveries. Risks from the force of contractions induced by Pitocin include potentially greater reductions in uterine blood flow than occur with natural contractions, which can lead to a greater reduction in oxygen for the fetus and possible fetal distress.

KEVIN FOLEY, RESEARCH/JULIE KELLER, DESIGN

KEVIN FOLEY, RESEARCH/JULIE KELLER, DESIGN

KEVIN FOLEY, RESEARCH/JULIE KELLER, DESIGN

PHOENIX, ARIZ. — The presence of an isolated intracardiac echogenic focus on fetal ultrasound does not increase the risk for aneuploidy in the absence of other risk factors in women younger than 35 years of age, Kathleen Bradley, M.D., reported at the annual meeting of the Pacific Coast Obstetrical and Gynecological Society.

Consequently, amniocentesis may not be indicated in these patients, she said.

Dr. Bradley and her associates conducted a study that involved 10,875 patients who had an ultrasound evaluation in the second trimester at Cedars-Sinai Medical Center, Los Angeles, from 1997 to 1999.

A total of 176 cases, or 1.6%, of fetal intracardiac echogenic foci (IEF) were identified. Among them, 80% had an isolated IEF finding, and 20% had other ultrasound findings.

Abnormal karyotypes were identified in the fetuses of three IEF patients. Each of the three patients was at least 35 years old. The three fetuses all had trisomy 21, according to Dr. Bradley, a perinatologist in Tarzana, Calif.

“Our findings suggest that there is not an increased risk of aneuploidy with isolated IEF where there are no other risk factors in women” aged 35 or younger, Dr. Bradley said at the meeting, which was cosponsored by the American College of Obstetricians and Gynecologists.

Dr. Bradley noted a larger study of 12,672 patients evaluated in the second trimester. There were 479 cases of IEF and 11 cases of trisomy 21. Only one fetus with trisomy 21 had an isolated echogenic focus (J. Ultrasound Med. 2004;23:489–96).

“These trends may be helpful for current clinical management,” Dr. Bradley said. She urged a move toward individualized risk assessment to include factors such as advanced maternal age, biochemical screening, and all ultrasound markers, given a relative risk for each soft marker.

“It is important to determine a critical cutoff level to offer invasive clinical diagnosis. Should we use the current age-based risk or the procedure-related risk?” she asked. In addition, Dr. Bradley noted that of the 97 patients involved in the study and who underwent amniocentesis, there were no procedure-related losses.

In a comment on the study, Roger Rowles, M.D., a Yakima, Wash., ob.gyn., emphasized that the findings, along with the larger study, offer important insights into the use of amniocentesis for isolated intracardiac echogenic foci.

“The reasonable conclusion is that finding an IEF should prompt a detailed anatomic survey and, in the absence of other ultrasound markers and risk factors, patients should not be offered amniocentesis,” he said.

PHOENIX, ARIZ. — The presence of an isolated intracardiac echogenic focus on fetal ultrasound does not increase the risk for aneuploidy in the absence of other risk factors in women younger than 35 years of age, Kathleen Bradley, M.D., reported at the annual meeting of the Pacific Coast Obstetrical and Gynecological Society.

Consequently, amniocentesis may not be indicated in these patients, she said.

Dr. Bradley and her associates conducted a study that involved 10,875 patients who had an ultrasound evaluation in the second trimester at Cedars-Sinai Medical Center, Los Angeles, from 1997 to 1999.

A total of 176 cases, or 1.6%, of fetal intracardiac echogenic foci (IEF) were identified. Among them, 80% had an isolated IEF finding, and 20% had other ultrasound findings.

Abnormal karyotypes were identified in the fetuses of three IEF patients. Each of the three patients was at least 35 years old. The three fetuses all had trisomy 21, according to Dr. Bradley, a perinatologist in Tarzana, Calif.

“Our findings suggest that there is not an increased risk of aneuploidy with isolated IEF where there are no other risk factors in women” aged 35 or younger, Dr. Bradley said at the meeting, which was cosponsored by the American College of Obstetricians and Gynecologists.

Dr. Bradley noted a larger study of 12,672 patients evaluated in the second trimester. There were 479 cases of IEF and 11 cases of trisomy 21. Only one fetus with trisomy 21 had an isolated echogenic focus (J. Ultrasound Med. 2004;23:489–96).

“These trends may be helpful for current clinical management,” Dr. Bradley said. She urged a move toward individualized risk assessment to include factors such as advanced maternal age, biochemical screening, and all ultrasound markers, given a relative risk for each soft marker.

“It is important to determine a critical cutoff level to offer invasive clinical diagnosis. Should we use the current age-based risk or the procedure-related risk?” she asked. In addition, Dr. Bradley noted that of the 97 patients involved in the study and who underwent amniocentesis, there were no procedure-related losses.

In a comment on the study, Roger Rowles, M.D., a Yakima, Wash., ob.gyn., emphasized that the findings, along with the larger study, offer important insights into the use of amniocentesis for isolated intracardiac echogenic foci.

“The reasonable conclusion is that finding an IEF should prompt a detailed anatomic survey and, in the absence of other ultrasound markers and risk factors, patients should not be offered amniocentesis,” he said.

PHOENIX, ARIZ. — The presence of an isolated intracardiac echogenic focus on fetal ultrasound does not increase the risk for aneuploidy in the absence of other risk factors in women younger than 35 years of age, Kathleen Bradley, M.D., reported at the annual meeting of the Pacific Coast Obstetrical and Gynecological Society.

Consequently, amniocentesis may not be indicated in these patients, she said.

Dr. Bradley and her associates conducted a study that involved 10,875 patients who had an ultrasound evaluation in the second trimester at Cedars-Sinai Medical Center, Los Angeles, from 1997 to 1999.

A total of 176 cases, or 1.6%, of fetal intracardiac echogenic foci (IEF) were identified. Among them, 80% had an isolated IEF finding, and 20% had other ultrasound findings.

Abnormal karyotypes were identified in the fetuses of three IEF patients. Each of the three patients was at least 35 years old. The three fetuses all had trisomy 21, according to Dr. Bradley, a perinatologist in Tarzana, Calif.

“Our findings suggest that there is not an increased risk of aneuploidy with isolated IEF where there are no other risk factors in women” aged 35 or younger, Dr. Bradley said at the meeting, which was cosponsored by the American College of Obstetricians and Gynecologists.

Dr. Bradley noted a larger study of 12,672 patients evaluated in the second trimester. There were 479 cases of IEF and 11 cases of trisomy 21. Only one fetus with trisomy 21 had an isolated echogenic focus (J. Ultrasound Med. 2004;23:489–96).

“These trends may be helpful for current clinical management,” Dr. Bradley said. She urged a move toward individualized risk assessment to include factors such as advanced maternal age, biochemical screening, and all ultrasound markers, given a relative risk for each soft marker.

“It is important to determine a critical cutoff level to offer invasive clinical diagnosis. Should we use the current age-based risk or the procedure-related risk?” she asked. In addition, Dr. Bradley noted that of the 97 patients involved in the study and who underwent amniocentesis, there were no procedure-related losses.

In a comment on the study, Roger Rowles, M.D., a Yakima, Wash., ob.gyn., emphasized that the findings, along with the larger study, offer important insights into the use of amniocentesis for isolated intracardiac echogenic foci.

“The reasonable conclusion is that finding an IEF should prompt a detailed anatomic survey and, in the absence of other ultrasound markers and risk factors, patients should not be offered amniocentesis,” he said.

VIENNA — Prolonged prednisolone administration reduces the risk of HELLP exacerbations in women undergoing expectant management remote from term, Pieter van Runnard Heimel, M.D., said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Previous studies have demonstrated a beneficial effect of corticosteroids during expectant management in women with early-onset preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Most of these studies, however, have not looked at antepartum treatment for longer than 48 hours, said Dr. Heimel of the department of perinatology and gynecology at the University Medical Center, Utrecht, the Netherlands.

Of 31 women who developed HELLP syndrome before 30 weeks' gestation and were being managed expectantly, 15 were given 50 mg intravenous prednisolone twice daily, while the other 16 received intravenous placebo. The two groups did not differ in maternal age, blood pressure, or worst laboratory values.

Delivery was postponed for about a week in both groups, and the mean interval between entry and delivery—6.9 days with prednisolone versus 8.0 days with placebo—was not significantly different. However, HELLP exacerbations occurred in just 6 prednisone patients, compared with 13 in the placebo group, a significant 50% relative risk reduction.

The number needed to treat to prevent one recurrent exacerbation, 2.4, was also significant, Dr. Heimel reported at the meeting.

Time to recovery of normal lab values differed significantly for platelets (1.7 days with prednisone vs. 6.2 days for placebo), but not for liver enzyme levels. There were no significant differences in cesarean section rates (15 in the prednisone group and 14 in the placebo group) or in fetal or maternal indications for cesarean section.

There were three maternal complications—liver hematoma, liver rupture, and liver rupture/maternal death—all in the placebo group.

Mean gestational age and birth weight were not significantly different between the two groups.

Four perinatal deaths occurred in the placebo group; two were fetal demise, and two were in newborns within the first week of life. Three infants in the prednisolone group died within the first year of life.

Ten infants from each group were still alive at 24 months. Of those, two from the prednisolone group had head circumferences less than 2 standard deviations below normal, while three from the prednisolone group and four from the placebo group had other abnormalities, according to Dr. Heimel.

VIENNA — Prolonged prednisolone administration reduces the risk of HELLP exacerbations in women undergoing expectant management remote from term, Pieter van Runnard Heimel, M.D., said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Previous studies have demonstrated a beneficial effect of corticosteroids during expectant management in women with early-onset preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Most of these studies, however, have not looked at antepartum treatment for longer than 48 hours, said Dr. Heimel of the department of perinatology and gynecology at the University Medical Center, Utrecht, the Netherlands.

Of 31 women who developed HELLP syndrome before 30 weeks' gestation and were being managed expectantly, 15 were given 50 mg intravenous prednisolone twice daily, while the other 16 received intravenous placebo. The two groups did not differ in maternal age, blood pressure, or worst laboratory values.

Delivery was postponed for about a week in both groups, and the mean interval between entry and delivery—6.9 days with prednisolone versus 8.0 days with placebo—was not significantly different. However, HELLP exacerbations occurred in just 6 prednisone patients, compared with 13 in the placebo group, a significant 50% relative risk reduction.

The number needed to treat to prevent one recurrent exacerbation, 2.4, was also significant, Dr. Heimel reported at the meeting.

Time to recovery of normal lab values differed significantly for platelets (1.7 days with prednisone vs. 6.2 days for placebo), but not for liver enzyme levels. There were no significant differences in cesarean section rates (15 in the prednisone group and 14 in the placebo group) or in fetal or maternal indications for cesarean section.

There were three maternal complications—liver hematoma, liver rupture, and liver rupture/maternal death—all in the placebo group.

Mean gestational age and birth weight were not significantly different between the two groups.

Four perinatal deaths occurred in the placebo group; two were fetal demise, and two were in newborns within the first week of life. Three infants in the prednisolone group died within the first year of life.

Ten infants from each group were still alive at 24 months. Of those, two from the prednisolone group had head circumferences less than 2 standard deviations below normal, while three from the prednisolone group and four from the placebo group had other abnormalities, according to Dr. Heimel.

VIENNA — Prolonged prednisolone administration reduces the risk of HELLP exacerbations in women undergoing expectant management remote from term, Pieter van Runnard Heimel, M.D., said at the 14th World Congress of the International Society for the Study of Hypertension in Pregnancy.

Previous studies have demonstrated a beneficial effect of corticosteroids during expectant management in women with early-onset preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Most of these studies, however, have not looked at antepartum treatment for longer than 48 hours, said Dr. Heimel of the department of perinatology and gynecology at the University Medical Center, Utrecht, the Netherlands.

Of 31 women who developed HELLP syndrome before 30 weeks' gestation and were being managed expectantly, 15 were given 50 mg intravenous prednisolone twice daily, while the other 16 received intravenous placebo. The two groups did not differ in maternal age, blood pressure, or worst laboratory values.

Delivery was postponed for about a week in both groups, and the mean interval between entry and delivery—6.9 days with prednisolone versus 8.0 days with placebo—was not significantly different. However, HELLP exacerbations occurred in just 6 prednisone patients, compared with 13 in the placebo group, a significant 50% relative risk reduction.

The number needed to treat to prevent one recurrent exacerbation, 2.4, was also significant, Dr. Heimel reported at the meeting.

Time to recovery of normal lab values differed significantly for platelets (1.7 days with prednisone vs. 6.2 days for placebo), but not for liver enzyme levels. There were no significant differences in cesarean section rates (15 in the prednisone group and 14 in the placebo group) or in fetal or maternal indications for cesarean section.

There were three maternal complications—liver hematoma, liver rupture, and liver rupture/maternal death—all in the placebo group.

Mean gestational age and birth weight were not significantly different between the two groups.

Four perinatal deaths occurred in the placebo group; two were fetal demise, and two were in newborns within the first week of life. Three infants in the prednisolone group died within the first year of life.

Ten infants from each group were still alive at 24 months. Of those, two from the prednisolone group had head circumferences less than 2 standard deviations below normal, while three from the prednisolone group and four from the placebo group had other abnormalities, according to Dr. Heimel.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity, she said.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder.

In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants who were exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their medication dosage and stop using the medication before conception.

If symptoms develop during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, Dr. Viguera said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation.

Valproic acid, on the other hand, is associated with a 3%–5% risk of a neural tube defect and an 8.9% risk for all anomalies, compared with a baseline rate of 2%–4%.

The risk of bipolar relapse during the postpartum period is very high, as is the risk for postpartum psychosis among women with bipolar disorder. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said.

“The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and other studies have suggested 24–48 hours post partum. In any case, Dr. Viguera said, “the post partum treatment plan should be addressed in advance.”

Treating Bipolar Issues in Pregnancy

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Recent studies have shown the teratogenicity rates are much lower than reported. The most common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. Valproate and carbamazepine have been linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as firstline therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in infants who were exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in infants who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic often is used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied as phenothiazine chlorpromazine.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been linked to significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine, is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety, according to Dr. Viguera.

Strategies for minimizing the risks associated with all of these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. She recommended that women taking anticonvulsants, in particular, take 4 mg of supplemental folic acid per day during the preconception period through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16–18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted.

In addition, because drug metabolism changes during pregnancy, both maternal and fetal serum drug levels should be monitored regularly.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity, she said.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder.

In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants who were exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their medication dosage and stop using the medication before conception.

If symptoms develop during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, Dr. Viguera said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation.

Valproic acid, on the other hand, is associated with a 3%–5% risk of a neural tube defect and an 8.9% risk for all anomalies, compared with a baseline rate of 2%–4%.

The risk of bipolar relapse during the postpartum period is very high, as is the risk for postpartum psychosis among women with bipolar disorder. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said.

“The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and other studies have suggested 24–48 hours post partum. In any case, Dr. Viguera said, “the post partum treatment plan should be addressed in advance.”

Treating Bipolar Issues in Pregnancy

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Recent studies have shown the teratogenicity rates are much lower than reported. The most common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. Valproate and carbamazepine have been linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as firstline therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in infants who were exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in infants who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic often is used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied as phenothiazine chlorpromazine.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been linked to significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine, is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety, according to Dr. Viguera.

Strategies for minimizing the risks associated with all of these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. She recommended that women taking anticonvulsants, in particular, take 4 mg of supplemental folic acid per day during the preconception period through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16–18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted.

In addition, because drug metabolism changes during pregnancy, both maternal and fetal serum drug levels should be monitored regularly.

BOSTON — Managing bipolar disorder during pregnancy requires balancing the competing risks and benefits to the woman and her fetus, said Adele Viguera, M.D.

“Pregnancy, and particularly the postpartum period, is associated with a high risk of disease recurrence for women with bipolar disorder,” said Dr. Viguera, director of the perinatal and reproductive psychiatry program at Massachusetts General Hospital in Boston. Although mood-stabilizing drugs can reduce this risk, most are associated with some degree of teratogenicity, she said.

Limited data exist to support the use in pregnancy of the mood stabilizers most commonly used to treat bipolar disorder.

In addition, mood stabilizers have been shown to increase the risk of certain types of birth defects or congenital malformations in infants who were exposed in utero, Dr. Viguera said during a meeting on bipolar disorder sponsored by Harvard Medical School.

To minimize the possibility of fetal damage, some women choose to discontinue their mood-stabilizing regimen, which itself markedly increases the risk of disease recurrence during pregnancy as well as postpartum illness. “More than half of women who discontinue treatment before or during pregnancy relapse, most frequently in the first trimester,” Dr. Viguera said.

The risks associated with treatment and treatment cessation vary considerably, depending on the nature and degree of illness and the agents used to treat it. “There is no single optimal management approach,” Dr. Viguera said. “Clinical management requires ongoing assessment of maternal and fetal status, risks, and benefits.”

Further complicating management is the fact that the Food and Drug Administration has not approved for use during pregnancy any of the psychotropic medications used to treat bipolar disease, because these agents diffuse across the placenta. The risk of birth defects depends on the drug used, when exposure occurs, and the duration of the exposure. It is generally understood that the highest risk to the fetus is during the first trimester, “but later exposure can also lead to malformations, behavioral effects, low birth weight, and preterm delivery,” Dr. Viguera said.

Women with bipolar disorder who have been stable for many years may be able to slowly decrease their medication dosage and stop using the medication before conception.

If symptoms develop during the first trimester, these women may be able to avoid using a mood stabilizer by treating some of the more troubling symptoms, such as irritability, insomnia, and hypomania, with an antipsychotic agent such as haloperidol or perphenazine. If symptoms appear after the first trimester, the mood stabilizer can be reintroduced with less risk of congenital malformation, Dr. Viguera said.

Among women who choose to continue a mood stabilizer during pregnancy to minimize the risk of recurrence, lithium appears to be the safest option. However, it is associated with a relatively small increased risk of a serious cardiac malformation.

Valproic acid, on the other hand, is associated with a 3%–5% risk of a neural tube defect and an 8.9% risk for all anomalies, compared with a baseline rate of 2%–4%.

The risk of bipolar relapse during the postpartum period is very high, as is the risk for postpartum psychosis among women with bipolar disorder. Consequently, medication prophylaxis generally is recommended, although there is some debate on timing, Dr. Viguera said.

“The goal is to maintain euthymia by reintroducing the mood stabilizer early,” she said. Some studies have shown benefits to reintroducing the drug in the third trimester, and other studies have suggested 24–48 hours post partum. In any case, Dr. Viguera said, “the post partum treatment plan should be addressed in advance.”

Treating Bipolar Issues in Pregnancy

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

▸ Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Recent studies have shown the teratogenicity rates are much lower than reported. The most common effects of fetal exposure are high birth weight and “floppy-baby” syndrome.

▸ Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. Valproate and carbamazepine have been linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as firstline therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in infants who were exposed in utero.

▸ Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in infants who have different antigen characteristics than their mothers.

▸ Chlorpromazine. This first-generation antipsychotic often is used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied as phenothiazine chlorpromazine.

▸ Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been linked to significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

▸ Olanzapine. One of the newer atypical antipsychotics, olanzapine, is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety, according to Dr. Viguera.

Strategies for minimizing the risks associated with all of these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation—in addition to a daily prenatal vitamin—may help reduce the increased risk of neural-tube defects. She recommended that women taking anticonvulsants, in particular, take 4 mg of supplemental folic acid per day during the preconception period through the first trimester.

“All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16–18 weeks to detect the presence of fetal malformations,” Dr. Viguera noted.

In addition, because drug metabolism changes during pregnancy, both maternal and fetal serum drug levels should be monitored regularly.