Obstetrics

Local and general anesthetic agents are commonly used in pregnancy, especially for epidural or combined spinal epidural analgesia at delivery. Although surgery requiring general anesthesia is less common, such use is still relatively frequent.

Local anesthetics are given by injection or topically, and include benzocaine, bupivacaine (Marcaine, Sensorcaine), chloroprocaine (Nesacaine), camphor, dibucaine (Nupercainal), levobupivacaine (Chirocaine), lidocaine (Xylocaine, Octocaine), mepivacaine (Carbocaine, Polocaine), pramoxine, prilocaine (Citanest), procaine (Novocaine), ropivacaine (Naropin), and tetracaine (Pontocaine). For neuraxial analgesia, low doses of bupivacaine, lidocaine, or ropivacaine – with or without a small dose of an opioid such as fentanyl – are commonly used. Use of injectable anesthetics for dental procedures also is common in pregnancy. Maternal toxicity involving the central nervous and cardiovascular systems may result from inadvertent intravenous administration or excessive doses.

Topical anesthetics are commonly used in dermatologic products; many are over-the-counter (OTC) products with multiple trade names not listed here. Such agents include benzocaine, butamben, cocaine, dibucaine, lidocaine, pramoxine, prilocaine, tetracaine, and dyclonine (a bactericidal and fungicidal local anesthetic used in lozenges and throat sprays for sore throats). The three topical cocaine products are controlled substances. Because of rapid absorption that can produce toxicity in the user, they are best avoided in pregnancy. Ethyl chloride (chloroethane) is a refrigerant used as a topical anesthetic. Although there are no reports of its use in pregnancy, the low absorption suggests that it is safe.

Benzocaine and pramoxine are available in OTC preparations for anorectal indications, such as hemorrhoids. The human pregnancy data are limited, but because there are more than 50 such products and hemorrhoids are common in pregnancy, these agents appear to be widely used in pregnancy. Systemic absorption may occur from mucous membranes or from damaged skin with the amount absorbed dependent on the dose.

The local anesthetics available for ophthalmic use are lidocaine (Akten), proparacaine (Alcaine, Ophthetic, Paracaine), proparacaine combined with fluorescein (Flucaine, Fluoracaine, Flurate, Fluress, Flurox), and tetracaine (Altacaine, Tetcaine).

In the above situations, with the exception of cocaine, the risk of any aspect of developmental toxicity from appropriate doses and administration of local anesthetics appears to be rare or nonexistent.

General anesthetics can be classified as injectable, gases, or volatile liquids. The injectable agents include droperidol (Inapsine), etomidate (Amidate), fospropofol (Lusedra), ketamine (Ketalar), methohexital (Brevital), midazolam (Versed), propofol (Diprivan), and sodium thiopental (Pentothal). The volatile liquids include desflurane (Suprane), enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), methoxyflurane (Penthrane), and sevoflurane (Ultane). All of the agents in these two categories of general anesthetics have the potential to cause neonatal depression or adverse neurobehavioral effects if used close to birth. For most agents, developmental toxicity during other periods of gestation, including organogenesis, has not been reported, but the human pregnancy experience is either absent or very limited. Moreover, the animal reproduction data, when these agents were used alone, were reassuring.

Because nitrous oxide is a gas, concerns have been raised about the potential for adverse effects on the embryo-fetus, as well as the potential effects on women of reproductive potential working in surgical areas. Moreover, when used for surgery, nitrous oxide is always combined with other general anesthetic agents. In animals, the gas is an embryo-fetal toxin (growth restriction, structural anomalies, and death), but the maternal exposures were sometimes high and prolonged. Long-lasting effects reported in animals include permanent brain damage resulting in abnormal behavior effects in motor development and general activity.

In humans, reports have described spontaneous abortions, infertility, and decreased birth weight in exposed pregnancies and in women of reproductive potential working in surgical areas and dental offices. Many of these retrospective reports were subject to self-reporting and/or recall bias, as well as confounders such as lack of information on exposure dose, type of anesthesia, use of other drugs, maternal age, and smoking. Scavenging and ventilating surgical rooms will lessen the exposure of personnel, but will not completely free the area of waste gases. Fortunately, the data do not support an association between acute or chronic nitrous oxide exposure and structural anomalies, but the news for neurotoxicity is troubling.

A 2004 study compared 40 children (ages 5–13 years) born to female physicians and nurses who were exposed to waste anesthetic gases (specific agents not identified) with 40 nonexposed controls matched for age, gender, and maternal occupation. The developmental milestones in the two groups were similar, but the exposed children had significantly lower gross motor ability and more evidence of inattention/hyperactivity. Moreover, the level of exposure was significantly and negatively correlated with fine motor ability and IQ performance (Birth Defects Res. A. Clin. Mol. Teratol. 2004;70:476–82). This study supported the hypothesis that occupational exposure to waste anesthetic gases during pregnancy might be a risk factor for minor neurological deficits in the offspring. Although more data are needed, women of reproductive potential working in surgical areas should consider decreasing or eliminating their exposure to anesthetic gases if pregnancy is a possibility. Moreover, postponing elective surgery until after pregnancy or, at least, after the period of organogenesis, also should be considered. Pregnancy tests should be conducted in any woman of reproductive potential before surgery.

Although the data are very limited, small amounts of some local anesthetics such as lidocaine are excreted into breast milk. Because the amounts in the maternal circulation are usually very low, any exposure of a nursing infant probably is clinically insignificant. Mothers exposed to general anesthetics will not be capable of nursing for several hours, thus allowing clearance of the agents from their circulation.

Local and general anesthetic agents are commonly used in pregnancy, especially for epidural or combined spinal epidural analgesia at delivery. Although surgery requiring general anesthesia is less common, such use is still relatively frequent.

Local anesthetics are given by injection or topically, and include benzocaine, bupivacaine (Marcaine, Sensorcaine), chloroprocaine (Nesacaine), camphor, dibucaine (Nupercainal), levobupivacaine (Chirocaine), lidocaine (Xylocaine, Octocaine), mepivacaine (Carbocaine, Polocaine), pramoxine, prilocaine (Citanest), procaine (Novocaine), ropivacaine (Naropin), and tetracaine (Pontocaine). For neuraxial analgesia, low doses of bupivacaine, lidocaine, or ropivacaine – with or without a small dose of an opioid such as fentanyl – are commonly used. Use of injectable anesthetics for dental procedures also is common in pregnancy. Maternal toxicity involving the central nervous and cardiovascular systems may result from inadvertent intravenous administration or excessive doses.

Topical anesthetics are commonly used in dermatologic products; many are over-the-counter (OTC) products with multiple trade names not listed here. Such agents include benzocaine, butamben, cocaine, dibucaine, lidocaine, pramoxine, prilocaine, tetracaine, and dyclonine (a bactericidal and fungicidal local anesthetic used in lozenges and throat sprays for sore throats). The three topical cocaine products are controlled substances. Because of rapid absorption that can produce toxicity in the user, they are best avoided in pregnancy. Ethyl chloride (chloroethane) is a refrigerant used as a topical anesthetic. Although there are no reports of its use in pregnancy, the low absorption suggests that it is safe.

Benzocaine and pramoxine are available in OTC preparations for anorectal indications, such as hemorrhoids. The human pregnancy data are limited, but because there are more than 50 such products and hemorrhoids are common in pregnancy, these agents appear to be widely used in pregnancy. Systemic absorption may occur from mucous membranes or from damaged skin with the amount absorbed dependent on the dose.

The local anesthetics available for ophthalmic use are lidocaine (Akten), proparacaine (Alcaine, Ophthetic, Paracaine), proparacaine combined with fluorescein (Flucaine, Fluoracaine, Flurate, Fluress, Flurox), and tetracaine (Altacaine, Tetcaine).

In the above situations, with the exception of cocaine, the risk of any aspect of developmental toxicity from appropriate doses and administration of local anesthetics appears to be rare or nonexistent.

General anesthetics can be classified as injectable, gases, or volatile liquids. The injectable agents include droperidol (Inapsine), etomidate (Amidate), fospropofol (Lusedra), ketamine (Ketalar), methohexital (Brevital), midazolam (Versed), propofol (Diprivan), and sodium thiopental (Pentothal). The volatile liquids include desflurane (Suprane), enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), methoxyflurane (Penthrane), and sevoflurane (Ultane). All of the agents in these two categories of general anesthetics have the potential to cause neonatal depression or adverse neurobehavioral effects if used close to birth. For most agents, developmental toxicity during other periods of gestation, including organogenesis, has not been reported, but the human pregnancy experience is either absent or very limited. Moreover, the animal reproduction data, when these agents were used alone, were reassuring.

Because nitrous oxide is a gas, concerns have been raised about the potential for adverse effects on the embryo-fetus, as well as the potential effects on women of reproductive potential working in surgical areas. Moreover, when used for surgery, nitrous oxide is always combined with other general anesthetic agents. In animals, the gas is an embryo-fetal toxin (growth restriction, structural anomalies, and death), but the maternal exposures were sometimes high and prolonged. Long-lasting effects reported in animals include permanent brain damage resulting in abnormal behavior effects in motor development and general activity.

In humans, reports have described spontaneous abortions, infertility, and decreased birth weight in exposed pregnancies and in women of reproductive potential working in surgical areas and dental offices. Many of these retrospective reports were subject to self-reporting and/or recall bias, as well as confounders such as lack of information on exposure dose, type of anesthesia, use of other drugs, maternal age, and smoking. Scavenging and ventilating surgical rooms will lessen the exposure of personnel, but will not completely free the area of waste gases. Fortunately, the data do not support an association between acute or chronic nitrous oxide exposure and structural anomalies, but the news for neurotoxicity is troubling.

A 2004 study compared 40 children (ages 5–13 years) born to female physicians and nurses who were exposed to waste anesthetic gases (specific agents not identified) with 40 nonexposed controls matched for age, gender, and maternal occupation. The developmental milestones in the two groups were similar, but the exposed children had significantly lower gross motor ability and more evidence of inattention/hyperactivity. Moreover, the level of exposure was significantly and negatively correlated with fine motor ability and IQ performance (Birth Defects Res. A. Clin. Mol. Teratol. 2004;70:476–82). This study supported the hypothesis that occupational exposure to waste anesthetic gases during pregnancy might be a risk factor for minor neurological deficits in the offspring. Although more data are needed, women of reproductive potential working in surgical areas should consider decreasing or eliminating their exposure to anesthetic gases if pregnancy is a possibility. Moreover, postponing elective surgery until after pregnancy or, at least, after the period of organogenesis, also should be considered. Pregnancy tests should be conducted in any woman of reproductive potential before surgery.

Although the data are very limited, small amounts of some local anesthetics such as lidocaine are excreted into breast milk. Because the amounts in the maternal circulation are usually very low, any exposure of a nursing infant probably is clinically insignificant. Mothers exposed to general anesthetics will not be capable of nursing for several hours, thus allowing clearance of the agents from their circulation.

Local and general anesthetic agents are commonly used in pregnancy, especially for epidural or combined spinal epidural analgesia at delivery. Although surgery requiring general anesthesia is less common, such use is still relatively frequent.

Local anesthetics are given by injection or topically, and include benzocaine, bupivacaine (Marcaine, Sensorcaine), chloroprocaine (Nesacaine), camphor, dibucaine (Nupercainal), levobupivacaine (Chirocaine), lidocaine (Xylocaine, Octocaine), mepivacaine (Carbocaine, Polocaine), pramoxine, prilocaine (Citanest), procaine (Novocaine), ropivacaine (Naropin), and tetracaine (Pontocaine). For neuraxial analgesia, low doses of bupivacaine, lidocaine, or ropivacaine – with or without a small dose of an opioid such as fentanyl – are commonly used. Use of injectable anesthetics for dental procedures also is common in pregnancy. Maternal toxicity involving the central nervous and cardiovascular systems may result from inadvertent intravenous administration or excessive doses.

Topical anesthetics are commonly used in dermatologic products; many are over-the-counter (OTC) products with multiple trade names not listed here. Such agents include benzocaine, butamben, cocaine, dibucaine, lidocaine, pramoxine, prilocaine, tetracaine, and dyclonine (a bactericidal and fungicidal local anesthetic used in lozenges and throat sprays for sore throats). The three topical cocaine products are controlled substances. Because of rapid absorption that can produce toxicity in the user, they are best avoided in pregnancy. Ethyl chloride (chloroethane) is a refrigerant used as a topical anesthetic. Although there are no reports of its use in pregnancy, the low absorption suggests that it is safe.

Benzocaine and pramoxine are available in OTC preparations for anorectal indications, such as hemorrhoids. The human pregnancy data are limited, but because there are more than 50 such products and hemorrhoids are common in pregnancy, these agents appear to be widely used in pregnancy. Systemic absorption may occur from mucous membranes or from damaged skin with the amount absorbed dependent on the dose.

The local anesthetics available for ophthalmic use are lidocaine (Akten), proparacaine (Alcaine, Ophthetic, Paracaine), proparacaine combined with fluorescein (Flucaine, Fluoracaine, Flurate, Fluress, Flurox), and tetracaine (Altacaine, Tetcaine).

In the above situations, with the exception of cocaine, the risk of any aspect of developmental toxicity from appropriate doses and administration of local anesthetics appears to be rare or nonexistent.

General anesthetics can be classified as injectable, gases, or volatile liquids. The injectable agents include droperidol (Inapsine), etomidate (Amidate), fospropofol (Lusedra), ketamine (Ketalar), methohexital (Brevital), midazolam (Versed), propofol (Diprivan), and sodium thiopental (Pentothal). The volatile liquids include desflurane (Suprane), enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), methoxyflurane (Penthrane), and sevoflurane (Ultane). All of the agents in these two categories of general anesthetics have the potential to cause neonatal depression or adverse neurobehavioral effects if used close to birth. For most agents, developmental toxicity during other periods of gestation, including organogenesis, has not been reported, but the human pregnancy experience is either absent or very limited. Moreover, the animal reproduction data, when these agents were used alone, were reassuring.

Because nitrous oxide is a gas, concerns have been raised about the potential for adverse effects on the embryo-fetus, as well as the potential effects on women of reproductive potential working in surgical areas. Moreover, when used for surgery, nitrous oxide is always combined with other general anesthetic agents. In animals, the gas is an embryo-fetal toxin (growth restriction, structural anomalies, and death), but the maternal exposures were sometimes high and prolonged. Long-lasting effects reported in animals include permanent brain damage resulting in abnormal behavior effects in motor development and general activity.

In humans, reports have described spontaneous abortions, infertility, and decreased birth weight in exposed pregnancies and in women of reproductive potential working in surgical areas and dental offices. Many of these retrospective reports were subject to self-reporting and/or recall bias, as well as confounders such as lack of information on exposure dose, type of anesthesia, use of other drugs, maternal age, and smoking. Scavenging and ventilating surgical rooms will lessen the exposure of personnel, but will not completely free the area of waste gases. Fortunately, the data do not support an association between acute or chronic nitrous oxide exposure and structural anomalies, but the news for neurotoxicity is troubling.

A 2004 study compared 40 children (ages 5–13 years) born to female physicians and nurses who were exposed to waste anesthetic gases (specific agents not identified) with 40 nonexposed controls matched for age, gender, and maternal occupation. The developmental milestones in the two groups were similar, but the exposed children had significantly lower gross motor ability and more evidence of inattention/hyperactivity. Moreover, the level of exposure was significantly and negatively correlated with fine motor ability and IQ performance (Birth Defects Res. A. Clin. Mol. Teratol. 2004;70:476–82). This study supported the hypothesis that occupational exposure to waste anesthetic gases during pregnancy might be a risk factor for minor neurological deficits in the offspring. Although more data are needed, women of reproductive potential working in surgical areas should consider decreasing or eliminating their exposure to anesthetic gases if pregnancy is a possibility. Moreover, postponing elective surgery until after pregnancy or, at least, after the period of organogenesis, also should be considered. Pregnancy tests should be conducted in any woman of reproductive potential before surgery.

Although the data are very limited, small amounts of some local anesthetics such as lidocaine are excreted into breast milk. Because the amounts in the maternal circulation are usually very low, any exposure of a nursing infant probably is clinically insignificant. Mothers exposed to general anesthetics will not be capable of nursing for several hours, thus allowing clearance of the agents from their circulation.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

Stroke may be an unusual event in pregnancy, but it’s becoming less of a rarity, according to a new study.¹ Hospitalizations related to stroke in pregnancy increased 54% over the past dozen years, from 4,085 in 1994–95 to 6,293 in 2006–07.

Researchers from the Centers for Disease Control and Prevention (CDC) analyzed a large national database of 5 to 8 million discharges from 1,000 hospitals and compared the rates of stroke from 1994–95 with the rates from 2006–07 in women who were pregnant, delivering a baby, and who had recently given birth.

In women who were pregnant, the rate of hospitalization for stroke rose 47%. The rate during the 12 weeks after delivery rose 83%. The rate remained stable for hospitalizations that occurred during the time immediately surrounding childbirth.

“I am surprised at the magnitude of the increase, which is substantial,” said Elena V. Kuklina, MD, PhD, lead author of the study and senior service fellow and epidemiologist at the CDC’s Division for Heart Disease and Stroke Prevention in Atlanta, Ga. “Our results indicate an urgent need to take a closer look. Stroke is such a debilitating condition. We need to put more effort into prevention.”

“Now more and more women entering pregnancy already have some type of risk factor for stroke, such as obesity, chronic hypertension, diabetes, or congenital heart disease. Since pregnancy by itself is a risk factor, if you have one of these other stroke risk factors, it doubles the risk.”

Not surprisingly, the prevalence of high blood pressure also rose over the 12-year period. In 1994–95, the rate was:

• 11.3% in antepartum women
• 23.4% in women at or near delivery
• 27.8% in women within 12 weeks after delivery.

In 2006–07, the rate was:

• 17% in antepartum women
• 28.5% in women at or near delivery
• 40.9% in women within 12 weeks after delivery.

“It’s best for women to enter pregnancy with ideal cardiovascular health, without additional risk factors,” Kuklina said. She recommends development of a comprehensive, multidisciplinary plan that gives doctors and patients guidelines for appropriate monitoring and care before, during, and after childbirth.

We want to hear from you! Tell us what you think.

Stroke may be an unusual event in pregnancy, but it’s becoming less of a rarity, according to a new study.¹ Hospitalizations related to stroke in pregnancy increased 54% over the past dozen years, from 4,085 in 1994–95 to 6,293 in 2006–07.

Researchers from the Centers for Disease Control and Prevention (CDC) analyzed a large national database of 5 to 8 million discharges from 1,000 hospitals and compared the rates of stroke from 1994–95 with the rates from 2006–07 in women who were pregnant, delivering a baby, and who had recently given birth.

In women who were pregnant, the rate of hospitalization for stroke rose 47%. The rate during the 12 weeks after delivery rose 83%. The rate remained stable for hospitalizations that occurred during the time immediately surrounding childbirth.

“I am surprised at the magnitude of the increase, which is substantial,” said Elena V. Kuklina, MD, PhD, lead author of the study and senior service fellow and epidemiologist at the CDC’s Division for Heart Disease and Stroke Prevention in Atlanta, Ga. “Our results indicate an urgent need to take a closer look. Stroke is such a debilitating condition. We need to put more effort into prevention.”

“Now more and more women entering pregnancy already have some type of risk factor for stroke, such as obesity, chronic hypertension, diabetes, or congenital heart disease. Since pregnancy by itself is a risk factor, if you have one of these other stroke risk factors, it doubles the risk.”

Not surprisingly, the prevalence of high blood pressure also rose over the 12-year period. In 1994–95, the rate was:

• 11.3% in antepartum women
• 23.4% in women at or near delivery
• 27.8% in women within 12 weeks after delivery.

In 2006–07, the rate was:

• 17% in antepartum women
• 28.5% in women at or near delivery
• 40.9% in women within 12 weeks after delivery.

“It’s best for women to enter pregnancy with ideal cardiovascular health, without additional risk factors,” Kuklina said. She recommends development of a comprehensive, multidisciplinary plan that gives doctors and patients guidelines for appropriate monitoring and care before, during, and after childbirth.

We want to hear from you! Tell us what you think.

Stroke may be an unusual event in pregnancy, but it’s becoming less of a rarity, according to a new study.¹ Hospitalizations related to stroke in pregnancy increased 54% over the past dozen years, from 4,085 in 1994–95 to 6,293 in 2006–07.

Researchers from the Centers for Disease Control and Prevention (CDC) analyzed a large national database of 5 to 8 million discharges from 1,000 hospitals and compared the rates of stroke from 1994–95 with the rates from 2006–07 in women who were pregnant, delivering a baby, and who had recently given birth.

In women who were pregnant, the rate of hospitalization for stroke rose 47%. The rate during the 12 weeks after delivery rose 83%. The rate remained stable for hospitalizations that occurred during the time immediately surrounding childbirth.

“I am surprised at the magnitude of the increase, which is substantial,” said Elena V. Kuklina, MD, PhD, lead author of the study and senior service fellow and epidemiologist at the CDC’s Division for Heart Disease and Stroke Prevention in Atlanta, Ga. “Our results indicate an urgent need to take a closer look. Stroke is such a debilitating condition. We need to put more effort into prevention.”

“Now more and more women entering pregnancy already have some type of risk factor for stroke, such as obesity, chronic hypertension, diabetes, or congenital heart disease. Since pregnancy by itself is a risk factor, if you have one of these other stroke risk factors, it doubles the risk.”

Not surprisingly, the prevalence of high blood pressure also rose over the 12-year period. In 1994–95, the rate was:

• 11.3% in antepartum women
• 23.4% in women at or near delivery
• 27.8% in women within 12 weeks after delivery.

In 2006–07, the rate was:

• 17% in antepartum women
• 28.5% in women at or near delivery
• 40.9% in women within 12 weeks after delivery.

“It’s best for women to enter pregnancy with ideal cardiovascular health, without additional risk factors,” Kuklina said. She recommends development of a comprehensive, multidisciplinary plan that gives doctors and patients guidelines for appropriate monitoring and care before, during, and after childbirth.

We want to hear from you! Tell us what you think.

Obstetric care providers have two patients: the mother and the fetus. Although it is relatively easy to tell when the mother is unwell, determining the well-being of the fetus is far more difficult.

Several tests have been developed to confirm fetal well-being during labor. The most widely used is electronic fetal heart rate monitoring (EFM), also referred to as fetal cardiotocography. EFM was introduced by Hon and Lee in the 1960s, and is now the most common obstetric procedure in the United States.^1,2 It is noninvasive, simple to perform, inexpensive, and readily available in almost all obstetric units. However, despite our best efforts, we have little objective evidence that EFM has improved perinatal outcomes.

A 2006 Cochrane review of 12 randomized, controlled trials (RCTs) involving more than 37,000 women concluded that, compared with intermittent auscultation—the only acceptable control because randomization to no intrapartum monitoring would be unethical—the only benefit of intrapartum EFM was a reduction in the incidence of seizures in the early neonatal period (the number needed to treat to prevent one event was 661). However, this finding did not translate into a diminished risk of seizures after the first week of life. There was otherwise no significant difference in perinatal outcomes, including no difference in the rates of cerebral palsy or death, although EFM was associated with an increased risk of obstetric intervention and operative delivery.³

It is this contradiction between the almost routine use of intrapartum EFM in the United States and the lack of evidence supporting its use that the authors hoped to address in their analysis.

What did Chen et al find?

In the lead-up to their analysis, the authors make a compelling argument that the existing data—including the 12 RCTs summarized in the Cochrane review³—are flawed. They raise specific concerns about such issues as “low-quality” study design, insufficient data in low-risk populations, and the use of pathologic antecedents (such as newborn encephalopathy) instead of cerebral palsy as a clinical endpoint. These are all reasonable and valid critiques.

So how did Chen and colleagues proceed? Did they design and execute a high-quality prospective study to address these issues? Did they reanalyze the existing RCTs using more sophisticated statistical methodology in an effort to correct for these deficiencies?

They did neither. They simply carried out another retrospective study using a large but poorly validated data set. In doing so, they transgressed and indeed aggravated all of the concerns they themselves raised about the existing literature. Specifically:

• Their retrospective analysis is a far inferior study design, compared with the RCTs they criticized
• Their efforts to distinguish between high-risk and low-risk pregnancies were rudimentary at best and relied on reported birth/death certificate data, which—as the authors themselves and the accompanying editorial concede⁴—is a notoriously unreliable source
• They made no effort to look at any medium- or long-term measures of neurologic injury.

The observation that EFM was associated with a decreased risk of neonatal seizures and 5-minute Apgar scores below 4 is not novel. Neither is the observation that EFM is associated with an increased risk of operative delivery—both cesarean and operative vaginal delivery. The only novel observation in this study is that, in a cohort of 1.7 million singleton pregnancies, EFM appeared to be associated with a decrease in the risk of early neonatal death (defined as death within the first 6 days of life), although no such association was noted for deaths in the late neonatal (7–27 days) or postneonatal (28–364 days) periods.

Limitations of the study design

RCTs remain the gold standard for clinical trials, and for good reason. The absence of randomization in the current study poses significant limitations. It prevents us from understanding why some women received intrapartum EFM while others did not. This makes it impossible to determine if we are comparing two equal groups, a limitation that cannot be overcome even with the most elegant of statistical analyses.

More concerning, however, is the lack of an adequate control group. The authors conclude that “the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity.” This begs the question: compared with what? In the numerous RCTs on this topic, intrapartum EFM was compared head-to-head with a standardized protocol of intermittent auscultation, whereas the comparison group in the current study was women who did not receive EFM.³ Stated differently, the absence of EFM is not equivalent to intermittent auscultation. An alternative and, in my opinion, far more likely explanation for the observed difference in mortality is that the current study compares women who received intrapartum EFM with those who simply had inadequate fetal monitoring in labor. And I am not aware of any report or, for that matter, any obstetric care provider who believes that it is unnecessary to monitor fetal well-being in labor.

The conclusion of this study should have been that adequate monitoring of the fetus in labor can prevent early neonatal death, not that adequate monitoring of the fetus in labor with EFM can prevent early neonatal death. Moreover, the authors’ attempt to deflect this issue by referring to the current study as an example of “reality-based medicine” as opposed to “evidence-based medicine” undermines the very foundation of scientific investigation.

More questions than answers

The major conclusion of this study is that EFM protects against early neonatal death. So why is there no information about cause of death? These data should be readily available from a linked birth/death certificate data set. Such information might help to determine whether the excess early neonatal deaths were related to EFM or, more likely, to other variables surrounding or related to the delivery, such as the inability to perform an emergency cesarean, if indicated, or the lack of providers skilled in neonatal resuscitation.

We want to hear from you!  Tell us what you think.

Obstetric care providers have two patients: the mother and the fetus. Although it is relatively easy to tell when the mother is unwell, determining the well-being of the fetus is far more difficult.

Several tests have been developed to confirm fetal well-being during labor. The most widely used is electronic fetal heart rate monitoring (EFM), also referred to as fetal cardiotocography. EFM was introduced by Hon and Lee in the 1960s, and is now the most common obstetric procedure in the United States.^1,2 It is noninvasive, simple to perform, inexpensive, and readily available in almost all obstetric units. However, despite our best efforts, we have little objective evidence that EFM has improved perinatal outcomes.

A 2006 Cochrane review of 12 randomized, controlled trials (RCTs) involving more than 37,000 women concluded that, compared with intermittent auscultation—the only acceptable control because randomization to no intrapartum monitoring would be unethical—the only benefit of intrapartum EFM was a reduction in the incidence of seizures in the early neonatal period (the number needed to treat to prevent one event was 661). However, this finding did not translate into a diminished risk of seizures after the first week of life. There was otherwise no significant difference in perinatal outcomes, including no difference in the rates of cerebral palsy or death, although EFM was associated with an increased risk of obstetric intervention and operative delivery.³

It is this contradiction between the almost routine use of intrapartum EFM in the United States and the lack of evidence supporting its use that the authors hoped to address in their analysis.

What did Chen et al find?

In the lead-up to their analysis, the authors make a compelling argument that the existing data—including the 12 RCTs summarized in the Cochrane review³—are flawed. They raise specific concerns about such issues as “low-quality” study design, insufficient data in low-risk populations, and the use of pathologic antecedents (such as newborn encephalopathy) instead of cerebral palsy as a clinical endpoint. These are all reasonable and valid critiques.

So how did Chen and colleagues proceed? Did they design and execute a high-quality prospective study to address these issues? Did they reanalyze the existing RCTs using more sophisticated statistical methodology in an effort to correct for these deficiencies?

They did neither. They simply carried out another retrospective study using a large but poorly validated data set. In doing so, they transgressed and indeed aggravated all of the concerns they themselves raised about the existing literature. Specifically:

• Their retrospective analysis is a far inferior study design, compared with the RCTs they criticized
• Their efforts to distinguish between high-risk and low-risk pregnancies were rudimentary at best and relied on reported birth/death certificate data, which—as the authors themselves and the accompanying editorial concede⁴—is a notoriously unreliable source
• They made no effort to look at any medium- or long-term measures of neurologic injury.

The observation that EFM was associated with a decreased risk of neonatal seizures and 5-minute Apgar scores below 4 is not novel. Neither is the observation that EFM is associated with an increased risk of operative delivery—both cesarean and operative vaginal delivery. The only novel observation in this study is that, in a cohort of 1.7 million singleton pregnancies, EFM appeared to be associated with a decrease in the risk of early neonatal death (defined as death within the first 6 days of life), although no such association was noted for deaths in the late neonatal (7–27 days) or postneonatal (28–364 days) periods.

Limitations of the study design

RCTs remain the gold standard for clinical trials, and for good reason. The absence of randomization in the current study poses significant limitations. It prevents us from understanding why some women received intrapartum EFM while others did not. This makes it impossible to determine if we are comparing two equal groups, a limitation that cannot be overcome even with the most elegant of statistical analyses.

More concerning, however, is the lack of an adequate control group. The authors conclude that “the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity.” This begs the question: compared with what? In the numerous RCTs on this topic, intrapartum EFM was compared head-to-head with a standardized protocol of intermittent auscultation, whereas the comparison group in the current study was women who did not receive EFM.³ Stated differently, the absence of EFM is not equivalent to intermittent auscultation. An alternative and, in my opinion, far more likely explanation for the observed difference in mortality is that the current study compares women who received intrapartum EFM with those who simply had inadequate fetal monitoring in labor. And I am not aware of any report or, for that matter, any obstetric care provider who believes that it is unnecessary to monitor fetal well-being in labor.

The conclusion of this study should have been that adequate monitoring of the fetus in labor can prevent early neonatal death, not that adequate monitoring of the fetus in labor with EFM can prevent early neonatal death. Moreover, the authors’ attempt to deflect this issue by referring to the current study as an example of “reality-based medicine” as opposed to “evidence-based medicine” undermines the very foundation of scientific investigation.

More questions than answers

The major conclusion of this study is that EFM protects against early neonatal death. So why is there no information about cause of death? These data should be readily available from a linked birth/death certificate data set. Such information might help to determine whether the excess early neonatal deaths were related to EFM or, more likely, to other variables surrounding or related to the delivery, such as the inability to perform an emergency cesarean, if indicated, or the lack of providers skilled in neonatal resuscitation.

We want to hear from you!  Tell us what you think.

Obstetric care providers have two patients: the mother and the fetus. Although it is relatively easy to tell when the mother is unwell, determining the well-being of the fetus is far more difficult.

Several tests have been developed to confirm fetal well-being during labor. The most widely used is electronic fetal heart rate monitoring (EFM), also referred to as fetal cardiotocography. EFM was introduced by Hon and Lee in the 1960s, and is now the most common obstetric procedure in the United States.^1,2 It is noninvasive, simple to perform, inexpensive, and readily available in almost all obstetric units. However, despite our best efforts, we have little objective evidence that EFM has improved perinatal outcomes.

A 2006 Cochrane review of 12 randomized, controlled trials (RCTs) involving more than 37,000 women concluded that, compared with intermittent auscultation—the only acceptable control because randomization to no intrapartum monitoring would be unethical—the only benefit of intrapartum EFM was a reduction in the incidence of seizures in the early neonatal period (the number needed to treat to prevent one event was 661). However, this finding did not translate into a diminished risk of seizures after the first week of life. There was otherwise no significant difference in perinatal outcomes, including no difference in the rates of cerebral palsy or death, although EFM was associated with an increased risk of obstetric intervention and operative delivery.³

It is this contradiction between the almost routine use of intrapartum EFM in the United States and the lack of evidence supporting its use that the authors hoped to address in their analysis.

What did Chen et al find?

In the lead-up to their analysis, the authors make a compelling argument that the existing data—including the 12 RCTs summarized in the Cochrane review³—are flawed. They raise specific concerns about such issues as “low-quality” study design, insufficient data in low-risk populations, and the use of pathologic antecedents (such as newborn encephalopathy) instead of cerebral palsy as a clinical endpoint. These are all reasonable and valid critiques.

So how did Chen and colleagues proceed? Did they design and execute a high-quality prospective study to address these issues? Did they reanalyze the existing RCTs using more sophisticated statistical methodology in an effort to correct for these deficiencies?

They did neither. They simply carried out another retrospective study using a large but poorly validated data set. In doing so, they transgressed and indeed aggravated all of the concerns they themselves raised about the existing literature. Specifically:

• Their retrospective analysis is a far inferior study design, compared with the RCTs they criticized
• Their efforts to distinguish between high-risk and low-risk pregnancies were rudimentary at best and relied on reported birth/death certificate data, which—as the authors themselves and the accompanying editorial concede⁴—is a notoriously unreliable source
• They made no effort to look at any medium- or long-term measures of neurologic injury.

The observation that EFM was associated with a decreased risk of neonatal seizures and 5-minute Apgar scores below 4 is not novel. Neither is the observation that EFM is associated with an increased risk of operative delivery—both cesarean and operative vaginal delivery. The only novel observation in this study is that, in a cohort of 1.7 million singleton pregnancies, EFM appeared to be associated with a decrease in the risk of early neonatal death (defined as death within the first 6 days of life), although no such association was noted for deaths in the late neonatal (7–27 days) or postneonatal (28–364 days) periods.

Limitations of the study design

RCTs remain the gold standard for clinical trials, and for good reason. The absence of randomization in the current study poses significant limitations. It prevents us from understanding why some women received intrapartum EFM while others did not. This makes it impossible to determine if we are comparing two equal groups, a limitation that cannot be overcome even with the most elegant of statistical analyses.

More concerning, however, is the lack of an adequate control group. The authors conclude that “the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity.” This begs the question: compared with what? In the numerous RCTs on this topic, intrapartum EFM was compared head-to-head with a standardized protocol of intermittent auscultation, whereas the comparison group in the current study was women who did not receive EFM.³ Stated differently, the absence of EFM is not equivalent to intermittent auscultation. An alternative and, in my opinion, far more likely explanation for the observed difference in mortality is that the current study compares women who received intrapartum EFM with those who simply had inadequate fetal monitoring in labor. And I am not aware of any report or, for that matter, any obstetric care provider who believes that it is unnecessary to monitor fetal well-being in labor.

The conclusion of this study should have been that adequate monitoring of the fetus in labor can prevent early neonatal death, not that adequate monitoring of the fetus in labor with EFM can prevent early neonatal death. Moreover, the authors’ attempt to deflect this issue by referring to the current study as an example of “reality-based medicine” as opposed to “evidence-based medicine” undermines the very foundation of scientific investigation.

More questions than answers

The major conclusion of this study is that EFM protects against early neonatal death. So why is there no information about cause of death? These data should be readily available from a linked birth/death certificate data set. Such information might help to determine whether the excess early neonatal deaths were related to EFM or, more likely, to other variables surrounding or related to the delivery, such as the inability to perform an emergency cesarean, if indicated, or the lack of providers skilled in neonatal resuscitation.

We want to hear from you!  Tell us what you think.

Major Finding: The positive predictive value of ultrasound-diagnosed fetal macrosomia, compared with actual macrosomia at birth, was just 37.4%.

Data Source: An observational cohort study of 235 pregnant women who had an ultrasound within 2 weeks of delivery indicating an estimated fetal weight of at least 4,500 g.

Disclosures: Dr. Wagner reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – An ultrasound diagnosis of fetal macrosomia at term is inaccurate in the majority of cases, and this inaccuracy may be contributing to unnecessary cesarean deliveries, new data suggest.

In an observational cohort study of 235 pregnancies at term in which US measurements led to a diagnosis of fetal macrosomia, only about a third of the infants were actually macrosomic at birth. Additionally, these pregnancies with US-diagnosed fetal macrosomia were more than twice as likely as all pregnancies in the population to end in cesarean delivery, according to results reported at the meeting.

US-estimated fetal weight “is not very accurate, and we have to counsel patients on that, when they come to ultrasounds and they are worried that they are going to have this [enormous] monstrosity of a baby,” lead investigator Dr. Alese Wagner said in an interview. “You can tell them [that] most of the time, we are off.”

She further recommended that physicians keep this new information in mind when it comes to recommending delivery interventions for a pregnancy in which the US suggests macrosomia.

Surprisingly, the accuracy of US in assessing fetal weight is similar to that of simple clinical palpation, according to Dr. Wagner, a third-year ob.gyn. resident at the University of Calgary in Alberta.

The study used the Hadlock formula for calculating weight from US fetal measurements, “which is supposed to be one of the better formulas for macrosomic infants,” she noted. But through the years, “as the technology has gotten better – these ultrasound machines that we have now are amazing [in] what they can do – this [accuracy] hasn't gotten better,” she added, speculating that the disconnect may in part be the result of reliance on simple measurements that don't take into account tissue densities.

Additionally, US assessment late in pregnancy is inherently more difficult because the fetus is so low in the pelvis and there is less amniotic fluid. Maternal body habitus also may play a role.

Using the clinical database of a tertiary referral center for the years 2005-2009, researchers identified 235 women who had a US exam within 2 weeks of delivery that indicated the presence of fetal macrosomia (defined as an estimated fetal weight of at least 4,500 g, as calculated via the Hadlock formula). However, they found that at delivery, only 88 of these infants had an actual birth weight of at least 4,500 g, for a positive predictive value of merely 37.4%, according to results reported in a poster session. The median estimated fetal weight was 4,693 g, whereas the median birth weight was 4,368 g.

The mean percentage error of the estimated fetal weight was 8.6% overall. Viewed another way, 44% of the weights were off by more than 10%, and 7% were off by more than 20%.

There were only weak correlations between estimated fetal weight and birth weight, as well as between the individual fetal measurements used in the Hadlock formula and birth weight.

The mode of delivery was cesarean section in 66% of the pregnancies, compared with just 29% of all pregnancies in Calgary during the same period. “So it's [more than] double, the percentage who are getting C-sections, on what is [an inaccurate weight],” said Dr. Wagner.

Before the study, “there was a general feeling that we were pretty [far off] in the estimates of the fetal weights that we were getting closer to term, especially for the bigger babies,” she commented. “People … usually thought that they were overestimating them, so it was nice to actually look at … what the actual numbers were.

Physicians can tell their worried patients that most of the time, the ultrasound calculations 'are off.'

Source DR. WAGNER

Major Finding: The positive predictive value of ultrasound-diagnosed fetal macrosomia, compared with actual macrosomia at birth, was just 37.4%.

Data Source: An observational cohort study of 235 pregnant women who had an ultrasound within 2 weeks of delivery indicating an estimated fetal weight of at least 4,500 g.

Disclosures: Dr. Wagner reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – An ultrasound diagnosis of fetal macrosomia at term is inaccurate in the majority of cases, and this inaccuracy may be contributing to unnecessary cesarean deliveries, new data suggest.

In an observational cohort study of 235 pregnancies at term in which US measurements led to a diagnosis of fetal macrosomia, only about a third of the infants were actually macrosomic at birth. Additionally, these pregnancies with US-diagnosed fetal macrosomia were more than twice as likely as all pregnancies in the population to end in cesarean delivery, according to results reported at the meeting.

US-estimated fetal weight “is not very accurate, and we have to counsel patients on that, when they come to ultrasounds and they are worried that they are going to have this [enormous] monstrosity of a baby,” lead investigator Dr. Alese Wagner said in an interview. “You can tell them [that] most of the time, we are off.”

She further recommended that physicians keep this new information in mind when it comes to recommending delivery interventions for a pregnancy in which the US suggests macrosomia.

Surprisingly, the accuracy of US in assessing fetal weight is similar to that of simple clinical palpation, according to Dr. Wagner, a third-year ob.gyn. resident at the University of Calgary in Alberta.

The study used the Hadlock formula for calculating weight from US fetal measurements, “which is supposed to be one of the better formulas for macrosomic infants,” she noted. But through the years, “as the technology has gotten better – these ultrasound machines that we have now are amazing [in] what they can do – this [accuracy] hasn't gotten better,” she added, speculating that the disconnect may in part be the result of reliance on simple measurements that don't take into account tissue densities.

Additionally, US assessment late in pregnancy is inherently more difficult because the fetus is so low in the pelvis and there is less amniotic fluid. Maternal body habitus also may play a role.

Using the clinical database of a tertiary referral center for the years 2005-2009, researchers identified 235 women who had a US exam within 2 weeks of delivery that indicated the presence of fetal macrosomia (defined as an estimated fetal weight of at least 4,500 g, as calculated via the Hadlock formula). However, they found that at delivery, only 88 of these infants had an actual birth weight of at least 4,500 g, for a positive predictive value of merely 37.4%, according to results reported in a poster session. The median estimated fetal weight was 4,693 g, whereas the median birth weight was 4,368 g.

The mean percentage error of the estimated fetal weight was 8.6% overall. Viewed another way, 44% of the weights were off by more than 10%, and 7% were off by more than 20%.

There were only weak correlations between estimated fetal weight and birth weight, as well as between the individual fetal measurements used in the Hadlock formula and birth weight.

The mode of delivery was cesarean section in 66% of the pregnancies, compared with just 29% of all pregnancies in Calgary during the same period. “So it's [more than] double, the percentage who are getting C-sections, on what is [an inaccurate weight],” said Dr. Wagner.

Before the study, “there was a general feeling that we were pretty [far off] in the estimates of the fetal weights that we were getting closer to term, especially for the bigger babies,” she commented. “People … usually thought that they were overestimating them, so it was nice to actually look at … what the actual numbers were.

Physicians can tell their worried patients that most of the time, the ultrasound calculations 'are off.'

Source DR. WAGNER

Major Finding: The positive predictive value of ultrasound-diagnosed fetal macrosomia, compared with actual macrosomia at birth, was just 37.4%.

Data Source: An observational cohort study of 235 pregnant women who had an ultrasound within 2 weeks of delivery indicating an estimated fetal weight of at least 4,500 g.

Disclosures: Dr. Wagner reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – An ultrasound diagnosis of fetal macrosomia at term is inaccurate in the majority of cases, and this inaccuracy may be contributing to unnecessary cesarean deliveries, new data suggest.

In an observational cohort study of 235 pregnancies at term in which US measurements led to a diagnosis of fetal macrosomia, only about a third of the infants were actually macrosomic at birth. Additionally, these pregnancies with US-diagnosed fetal macrosomia were more than twice as likely as all pregnancies in the population to end in cesarean delivery, according to results reported at the meeting.

US-estimated fetal weight “is not very accurate, and we have to counsel patients on that, when they come to ultrasounds and they are worried that they are going to have this [enormous] monstrosity of a baby,” lead investigator Dr. Alese Wagner said in an interview. “You can tell them [that] most of the time, we are off.”

She further recommended that physicians keep this new information in mind when it comes to recommending delivery interventions for a pregnancy in which the US suggests macrosomia.

Surprisingly, the accuracy of US in assessing fetal weight is similar to that of simple clinical palpation, according to Dr. Wagner, a third-year ob.gyn. resident at the University of Calgary in Alberta.

The study used the Hadlock formula for calculating weight from US fetal measurements, “which is supposed to be one of the better formulas for macrosomic infants,” she noted. But through the years, “as the technology has gotten better – these ultrasound machines that we have now are amazing [in] what they can do – this [accuracy] hasn't gotten better,” she added, speculating that the disconnect may in part be the result of reliance on simple measurements that don't take into account tissue densities.

Additionally, US assessment late in pregnancy is inherently more difficult because the fetus is so low in the pelvis and there is less amniotic fluid. Maternal body habitus also may play a role.

Using the clinical database of a tertiary referral center for the years 2005-2009, researchers identified 235 women who had a US exam within 2 weeks of delivery that indicated the presence of fetal macrosomia (defined as an estimated fetal weight of at least 4,500 g, as calculated via the Hadlock formula). However, they found that at delivery, only 88 of these infants had an actual birth weight of at least 4,500 g, for a positive predictive value of merely 37.4%, according to results reported in a poster session. The median estimated fetal weight was 4,693 g, whereas the median birth weight was 4,368 g.

The mean percentage error of the estimated fetal weight was 8.6% overall. Viewed another way, 44% of the weights were off by more than 10%, and 7% were off by more than 20%.

There were only weak correlations between estimated fetal weight and birth weight, as well as between the individual fetal measurements used in the Hadlock formula and birth weight.

The mode of delivery was cesarean section in 66% of the pregnancies, compared with just 29% of all pregnancies in Calgary during the same period. “So it's [more than] double, the percentage who are getting C-sections, on what is [an inaccurate weight],” said Dr. Wagner.

Before the study, “there was a general feeling that we were pretty [far off] in the estimates of the fetal weights that we were getting closer to term, especially for the bigger babies,” she commented. “People … usually thought that they were overestimating them, so it was nice to actually look at … what the actual numbers were.

Physicians can tell their worried patients that most of the time, the ultrasound calculations 'are off.'

Source DR. WAGNER

Major Finding: In screening for sleep apnea via prepregnancy BMI plus self-reported snoring, sensitivity was 74% and specificity was 59%, compared with 35% and 69% for standard screening measures.

Data Source: A prospective study comparing the accuracy of standard sleep apnea screening measures to a two-question approach based on prepregnancy BMI and self-reported snoring in 86 women with high-risk pregnancies.

Disclosures: Dr. Facco reported having no financial conflicts.

MINNEAPOLIS – A two-question screening tool for sleep apnea yielded more accurate results than did standard screening tools, a study has shown.

“Using prepregnancy body mass index and self-reported snoring had a much better sensitivity than the conventional methods, without sacrificing much specificity,” Dr. Francesca L. Facco reported at the meeting.

In a cohort of pregnant women who completed a sleep survey and participated in an overnight sleep evaluation, the two-question screening approach yielded more accurate results than did standard screening tools, including the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS), she said.

To compare the screening approaches, Dr. Facco of the department of ob.gyn. at Northwestern University, Chicago, and her colleagues recruited 86 high-risk pregnant women, including those with chronic hypertension, pregestational diabetes, obesity, or a prior history of preeclampsia, to complete the sleep survey, which consisted of the BQ and ESS measures.

The women also underwent an overnight sleep evaluation using Itamar Medical's Watch-PAT100 (WP100), a wrist-mounted, ambulatory device designed to diagnose sleep apnea, Dr. Facco said.

For this study, sleep apnea was defined as an apnea-hypopnea index score of five or more episodes of disturbed sleep per hour.

Patients' prepregnancy BMI and self-reporting snoring status were recorded as well.

“Patients with a prepregnancy BMI of 25 [kg/m

The investigators assessed the performance of the BQ, ESS, and two-question measures relative to the data acquired from the WP100 devices using receiver operating characteristic (ROC) curves, and determined that the two-question approach performed better than the BQ alone, the BQ and ESS combined, and the null hypothesis, according to Dr. Facco.

The sensitivity of the combined BQ and ESS was 35% and the specificity was 69%, compared with 74% and 59%, respectively, for the two-question approach. “The results suggest that standard screening tools for sleep apnea, which have a high sensitivity and specificity in nonpregnant individuals, are inadequate for the assessment of sleep apnea in pregnancy,” Dr. Facco said.

Modifications that take into account the predictive value of prepregnancy BMI and snoring are warranted, she said, stressing that additional studies are needed to design and test the most appropriate measure for sleep apnea screening in pregnancy.

Because sleep apnea may be associated with complications during pregnancy and with adverse pregnancy outcomes, screening for the disorder should be considered for all pregnant women, and particularly those who are considered to be at high risk, Dr. Facco noted.

Major Finding: In screening for sleep apnea via prepregnancy BMI plus self-reported snoring, sensitivity was 74% and specificity was 59%, compared with 35% and 69% for standard screening measures.

Data Source: A prospective study comparing the accuracy of standard sleep apnea screening measures to a two-question approach based on prepregnancy BMI and self-reported snoring in 86 women with high-risk pregnancies.

Disclosures: Dr. Facco reported having no financial conflicts.

MINNEAPOLIS – A two-question screening tool for sleep apnea yielded more accurate results than did standard screening tools, a study has shown.

“Using prepregnancy body mass index and self-reported snoring had a much better sensitivity than the conventional methods, without sacrificing much specificity,” Dr. Francesca L. Facco reported at the meeting.

In a cohort of pregnant women who completed a sleep survey and participated in an overnight sleep evaluation, the two-question screening approach yielded more accurate results than did standard screening tools, including the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS), she said.

To compare the screening approaches, Dr. Facco of the department of ob.gyn. at Northwestern University, Chicago, and her colleagues recruited 86 high-risk pregnant women, including those with chronic hypertension, pregestational diabetes, obesity, or a prior history of preeclampsia, to complete the sleep survey, which consisted of the BQ and ESS measures.

The women also underwent an overnight sleep evaluation using Itamar Medical's Watch-PAT100 (WP100), a wrist-mounted, ambulatory device designed to diagnose sleep apnea, Dr. Facco said.

For this study, sleep apnea was defined as an apnea-hypopnea index score of five or more episodes of disturbed sleep per hour.

Patients' prepregnancy BMI and self-reporting snoring status were recorded as well.

“Patients with a prepregnancy BMI of 25 [kg/m

The investigators assessed the performance of the BQ, ESS, and two-question measures relative to the data acquired from the WP100 devices using receiver operating characteristic (ROC) curves, and determined that the two-question approach performed better than the BQ alone, the BQ and ESS combined, and the null hypothesis, according to Dr. Facco.

The sensitivity of the combined BQ and ESS was 35% and the specificity was 69%, compared with 74% and 59%, respectively, for the two-question approach. “The results suggest that standard screening tools for sleep apnea, which have a high sensitivity and specificity in nonpregnant individuals, are inadequate for the assessment of sleep apnea in pregnancy,” Dr. Facco said.

Modifications that take into account the predictive value of prepregnancy BMI and snoring are warranted, she said, stressing that additional studies are needed to design and test the most appropriate measure for sleep apnea screening in pregnancy.

Because sleep apnea may be associated with complications during pregnancy and with adverse pregnancy outcomes, screening for the disorder should be considered for all pregnant women, and particularly those who are considered to be at high risk, Dr. Facco noted.

Major Finding: In screening for sleep apnea via prepregnancy BMI plus self-reported snoring, sensitivity was 74% and specificity was 59%, compared with 35% and 69% for standard screening measures.

Data Source: A prospective study comparing the accuracy of standard sleep apnea screening measures to a two-question approach based on prepregnancy BMI and self-reported snoring in 86 women with high-risk pregnancies.

Disclosures: Dr. Facco reported having no financial conflicts.

MINNEAPOLIS – A two-question screening tool for sleep apnea yielded more accurate results than did standard screening tools, a study has shown.

“Using prepregnancy body mass index and self-reported snoring had a much better sensitivity than the conventional methods, without sacrificing much specificity,” Dr. Francesca L. Facco reported at the meeting.

In a cohort of pregnant women who completed a sleep survey and participated in an overnight sleep evaluation, the two-question screening approach yielded more accurate results than did standard screening tools, including the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS), she said.

To compare the screening approaches, Dr. Facco of the department of ob.gyn. at Northwestern University, Chicago, and her colleagues recruited 86 high-risk pregnant women, including those with chronic hypertension, pregestational diabetes, obesity, or a prior history of preeclampsia, to complete the sleep survey, which consisted of the BQ and ESS measures.

The women also underwent an overnight sleep evaluation using Itamar Medical's Watch-PAT100 (WP100), a wrist-mounted, ambulatory device designed to diagnose sleep apnea, Dr. Facco said.

For this study, sleep apnea was defined as an apnea-hypopnea index score of five or more episodes of disturbed sleep per hour.

Patients' prepregnancy BMI and self-reporting snoring status were recorded as well.

“Patients with a prepregnancy BMI of 25 [kg/m

The investigators assessed the performance of the BQ, ESS, and two-question measures relative to the data acquired from the WP100 devices using receiver operating characteristic (ROC) curves, and determined that the two-question approach performed better than the BQ alone, the BQ and ESS combined, and the null hypothesis, according to Dr. Facco.

The sensitivity of the combined BQ and ESS was 35% and the specificity was 69%, compared with 74% and 59%, respectively, for the two-question approach. “The results suggest that standard screening tools for sleep apnea, which have a high sensitivity and specificity in nonpregnant individuals, are inadequate for the assessment of sleep apnea in pregnancy,” Dr. Facco said.

Modifications that take into account the predictive value of prepregnancy BMI and snoring are warranted, she said, stressing that additional studies are needed to design and test the most appropriate measure for sleep apnea screening in pregnancy.

Because sleep apnea may be associated with complications during pregnancy and with adverse pregnancy outcomes, screening for the disorder should be considered for all pregnant women, and particularly those who are considered to be at high risk, Dr. Facco noted.

Major Finding: In the no, mild, and moderate to severe sleep disordered breathing groups, the composite adverse pregnancy outcome rates were 18.1%, 23.5%, and 38.5%, respectively.

Data Source: A retrospective cohort study to assess the association between sleep-disordered breathing and adverse pregnancy outcomes in 150 women who had a delivery and an in-laboratory polysomnogram between January 2000 and June 2009.

Disclosures: Dr. Facco said she had no relevant financial disclosures.

MINNEAPOLIS – Women with sleep-disordered breathing have an increased likelihood of adverse pregnancy outcomes, but it is unclear whether the heightened risk can be attributed primarily to the breathing disorder or to obesity, reported lead investigator Dr. Francesca L. Facco.

Sleep disordered breathing (SDB) occurs in approximately 2% of the female population and has been linked to cardiovascular and metabolic morbidities and mortality in nonpregnant populations, said Dr. Facco of the department of ob.gyn. at Northwestern University in Chicago. “There is some evidence that pregnancy may precipitate or exacerbate the condition, and that there may be a relationship between intrauterine fetal growth retardation and maternal preeclampsia.” Unfortunately, “few studies have examined the relationship between abnormal respiratory patterns or quality of ventilation during sleep in pregnancy and adverse obstetrical outcomes, which is what we sought to do in this investigation” she said at the meeting.

Toward this end, Dr. Facco and her colleagues conducted a retrospective cohort study, using ICD-9 codes to identify women who had a delivery and an in-laboratory polysomnogram at their institution between January 2000 and June 2009. They reviewed the medical charts of 150 patients and abstracted data on demographics, sleep study results, and pregnancy outcomes. “In women with more than one pregnancy, we looked at the first pregnancy with outcome information,” she explained.

The study's primary outcome was adverse pregnancy outcome, which was defined as pregnancy-induced hypertension, gestational diabetes, and early preterm birth (at or before 34 weeks' gestation), Dr. Facco said.

The apnea-hypopnea index (AHI) was used to classify the presence and degree of SDB, with an AHI of fewer than 5 breathing pauses per hour indicating no SDB, an AHI of 5-14.9 pauses per hour indicating mild to moderate SDB, and an AHI of 15 or more pauses per hour suggesting a severe condition, she said. The associations between SBD and adverse pregnancy outcomes were evaluated using a Chi-square test for trend.

Of the 150 women included in the investigation, 61% were nulliparous at the time of their first documented delivery at the study hospital, 72% had undergone a polysomnogram within 3 years of their delivery, and 86.7% were overweight or obese (defined as a body mass index of 25 kg/m

An analysis of the findings demonstrated a significant association between SDB and adverse pregnancy outcome.

“The incidence of adverse pregnancy outcomes was highest in women with severe sleep apnea,” she said, noting that the increased prevalence was principally driven by a higher incidence of gestational diabetes and early preterm birth.

In the no, mild, and moderate to severe SDB groups, respectively, researchers found the following:

▸ The composite adverse pregnancy outcome rates were 18.1%, 23.5%, and 38.5%.

▸ The gestational diabetes rates were 0%, 5.9%, and 11.5%.

▸ The preterm birth rates were 4.7%, 5.9%, and 15.4%.

▸ The pregnancy-induced hypertension rates were 16.9%, 17.6%, and 15.4%.

“Gestational diabetes has been independently associated with maternal obesity, as has preterm birth and low birth weight,” Dr. Facco said in an interview. “In this population, nearly 87% of the women who had [SDB] were also obese, making it an obvious confounding factor.”

Further prospective studies are needed to assess the independent impact of SDB on maternal and neonatal health, and if the independent association is confirmed, additional studies on the role of treatment in pregnancy would be needed, Dr. Facco said.

In this population, nearly 87% of the women who had sleep disordered breathing were also obese, making it an obvious confounding factor.

Source Catherine Harrell/Elsevier Global Medical News

Major Finding: In the no, mild, and moderate to severe sleep disordered breathing groups, the composite adverse pregnancy outcome rates were 18.1%, 23.5%, and 38.5%, respectively.

Data Source: A retrospective cohort study to assess the association between sleep-disordered breathing and adverse pregnancy outcomes in 150 women who had a delivery and an in-laboratory polysomnogram between January 2000 and June 2009.

Disclosures: Dr. Facco said she had no relevant financial disclosures.

MINNEAPOLIS – Women with sleep-disordered breathing have an increased likelihood of adverse pregnancy outcomes, but it is unclear whether the heightened risk can be attributed primarily to the breathing disorder or to obesity, reported lead investigator Dr. Francesca L. Facco.

Sleep disordered breathing (SDB) occurs in approximately 2% of the female population and has been linked to cardiovascular and metabolic morbidities and mortality in nonpregnant populations, said Dr. Facco of the department of ob.gyn. at Northwestern University in Chicago. “There is some evidence that pregnancy may precipitate or exacerbate the condition, and that there may be a relationship between intrauterine fetal growth retardation and maternal preeclampsia.” Unfortunately, “few studies have examined the relationship between abnormal respiratory patterns or quality of ventilation during sleep in pregnancy and adverse obstetrical outcomes, which is what we sought to do in this investigation” she said at the meeting.

Toward this end, Dr. Facco and her colleagues conducted a retrospective cohort study, using ICD-9 codes to identify women who had a delivery and an in-laboratory polysomnogram at their institution between January 2000 and June 2009. They reviewed the medical charts of 150 patients and abstracted data on demographics, sleep study results, and pregnancy outcomes. “In women with more than one pregnancy, we looked at the first pregnancy with outcome information,” she explained.

The study's primary outcome was adverse pregnancy outcome, which was defined as pregnancy-induced hypertension, gestational diabetes, and early preterm birth (at or before 34 weeks' gestation), Dr. Facco said.

The apnea-hypopnea index (AHI) was used to classify the presence and degree of SDB, with an AHI of fewer than 5 breathing pauses per hour indicating no SDB, an AHI of 5-14.9 pauses per hour indicating mild to moderate SDB, and an AHI of 15 or more pauses per hour suggesting a severe condition, she said. The associations between SBD and adverse pregnancy outcomes were evaluated using a Chi-square test for trend.

Of the 150 women included in the investigation, 61% were nulliparous at the time of their first documented delivery at the study hospital, 72% had undergone a polysomnogram within 3 years of their delivery, and 86.7% were overweight or obese (defined as a body mass index of 25 kg/m

An analysis of the findings demonstrated a significant association between SDB and adverse pregnancy outcome.

“The incidence of adverse pregnancy outcomes was highest in women with severe sleep apnea,” she said, noting that the increased prevalence was principally driven by a higher incidence of gestational diabetes and early preterm birth.

In the no, mild, and moderate to severe SDB groups, respectively, researchers found the following:

▸ The composite adverse pregnancy outcome rates were 18.1%, 23.5%, and 38.5%.

▸ The gestational diabetes rates were 0%, 5.9%, and 11.5%.

▸ The preterm birth rates were 4.7%, 5.9%, and 15.4%.

▸ The pregnancy-induced hypertension rates were 16.9%, 17.6%, and 15.4%.

“Gestational diabetes has been independently associated with maternal obesity, as has preterm birth and low birth weight,” Dr. Facco said in an interview. “In this population, nearly 87% of the women who had [SDB] were also obese, making it an obvious confounding factor.”

Further prospective studies are needed to assess the independent impact of SDB on maternal and neonatal health, and if the independent association is confirmed, additional studies on the role of treatment in pregnancy would be needed, Dr. Facco said.

In this population, nearly 87% of the women who had sleep disordered breathing were also obese, making it an obvious confounding factor.

Source Catherine Harrell/Elsevier Global Medical News

Major Finding: In the no, mild, and moderate to severe sleep disordered breathing groups, the composite adverse pregnancy outcome rates were 18.1%, 23.5%, and 38.5%, respectively.

Data Source: A retrospective cohort study to assess the association between sleep-disordered breathing and adverse pregnancy outcomes in 150 women who had a delivery and an in-laboratory polysomnogram between January 2000 and June 2009.

Disclosures: Dr. Facco said she had no relevant financial disclosures.

MINNEAPOLIS – Women with sleep-disordered breathing have an increased likelihood of adverse pregnancy outcomes, but it is unclear whether the heightened risk can be attributed primarily to the breathing disorder or to obesity, reported lead investigator Dr. Francesca L. Facco.

Sleep disordered breathing (SDB) occurs in approximately 2% of the female population and has been linked to cardiovascular and metabolic morbidities and mortality in nonpregnant populations, said Dr. Facco of the department of ob.gyn. at Northwestern University in Chicago. “There is some evidence that pregnancy may precipitate or exacerbate the condition, and that there may be a relationship between intrauterine fetal growth retardation and maternal preeclampsia.” Unfortunately, “few studies have examined the relationship between abnormal respiratory patterns or quality of ventilation during sleep in pregnancy and adverse obstetrical outcomes, which is what we sought to do in this investigation” she said at the meeting.

Toward this end, Dr. Facco and her colleagues conducted a retrospective cohort study, using ICD-9 codes to identify women who had a delivery and an in-laboratory polysomnogram at their institution between January 2000 and June 2009. They reviewed the medical charts of 150 patients and abstracted data on demographics, sleep study results, and pregnancy outcomes. “In women with more than one pregnancy, we looked at the first pregnancy with outcome information,” she explained.

The study's primary outcome was adverse pregnancy outcome, which was defined as pregnancy-induced hypertension, gestational diabetes, and early preterm birth (at or before 34 weeks' gestation), Dr. Facco said.

The apnea-hypopnea index (AHI) was used to classify the presence and degree of SDB, with an AHI of fewer than 5 breathing pauses per hour indicating no SDB, an AHI of 5-14.9 pauses per hour indicating mild to moderate SDB, and an AHI of 15 or more pauses per hour suggesting a severe condition, she said. The associations between SBD and adverse pregnancy outcomes were evaluated using a Chi-square test for trend.

Of the 150 women included in the investigation, 61% were nulliparous at the time of their first documented delivery at the study hospital, 72% had undergone a polysomnogram within 3 years of their delivery, and 86.7% were overweight or obese (defined as a body mass index of 25 kg/m

An analysis of the findings demonstrated a significant association between SDB and adverse pregnancy outcome.

“The incidence of adverse pregnancy outcomes was highest in women with severe sleep apnea,” she said, noting that the increased prevalence was principally driven by a higher incidence of gestational diabetes and early preterm birth.

In the no, mild, and moderate to severe SDB groups, respectively, researchers found the following:

▸ The composite adverse pregnancy outcome rates were 18.1%, 23.5%, and 38.5%.

▸ The gestational diabetes rates were 0%, 5.9%, and 11.5%.

▸ The preterm birth rates were 4.7%, 5.9%, and 15.4%.

▸ The pregnancy-induced hypertension rates were 16.9%, 17.6%, and 15.4%.

“Gestational diabetes has been independently associated with maternal obesity, as has preterm birth and low birth weight,” Dr. Facco said in an interview. “In this population, nearly 87% of the women who had [SDB] were also obese, making it an obvious confounding factor.”

Further prospective studies are needed to assess the independent impact of SDB on maternal and neonatal health, and if the independent association is confirmed, additional studies on the role of treatment in pregnancy would be needed, Dr. Facco said.

In this population, nearly 87% of the women who had sleep disordered breathing were also obese, making it an obvious confounding factor.

Source Catherine Harrell/Elsevier Global Medical News

Major Finding: The negative predictive values for preterm delivery were similarly high for ph IGFBP-1 and fetal fibronectin; the positive predictive values were poor for both.

Data Source: A prospective cohort study among 349 women with symptoms of preterm labor.

Disclosures: Dr. Cooper reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – The phosphorylated insulinlike growth factor binding protein–1 test may edge out the fetal fibronectin test when it comes to predicting preterm delivery, a study has shown.

In the prospective cohort study among 349 women with symptoms of preterm labor, the two tests had similarly good negative predictive values, 0.86 and 0.88, researchers reported at the meeting. Both had poor sensitivity and positive predictive values.

However, the phosphorylated insulinlike growth factor binding protein–1 (ph IGFBP-1) test (marketed outside the United States as the Actim Partus test) costs about one-fourth as much as the fetal fibronectin test. Also, the former is a simple dipstick test that can be run at the bedside, and it differs in not being affected by recent intercourse or vaginal examinations.

The Actim Partus test is not currently available in the United States. “The timeline for its clearance and availability in the United States is … not yet known,” according to a spokeswoman for Medix Biochemica, Kauniainen, Finland.

“The Actim Partus compares favorably to fetal fibronectin for the ability to rule out preterm labor,” said lead investigator Dr. Stephanie Cooper, program director of maternal-fetal medicine at the University of Calgary (Alta.). “Given the benefit of reduced cost, efficiency, and ability to use it in a broad clinical scenario, institutions should consider using the newer test, the Partus test, until better tools are available.”

Her institution has not yet switched to the new test. “But what I will say is these results definitely make me do fetal fibronectin less,” she commented. “I don't think Partus is a good test, I don't think fibronectin is a good test. … I'm hoping that there's going to be a better test.”

Fetal fibronectin is generally regarded as the gold standard for predicting preterm delivery, according to Dr. Cooper.

However, “it is not a perfect test. In fact, maybe it's more like the bronze standard,” she commented. Its limitations include a poor positive predictive value; false-positivity in women who have recently had a vaginal exam or intercourse; cost; and, usually, the need for a laboratory for analysis.

“Ph IGFBP-1 is released by the cervix following disruption of the choriodecidual barrier, which we believe occurs with the onset of labor,” she explained. It has shown promise for overcoming some of the limitations of the fetal fibronectin test.

The researchers enrolled in the study 349 women who had symptoms of labor preterm (between 24 and 34 weeks' gestation) and no contraindications to vaginal examination.

Women were ineligible if they had ruptured membranes, had antepartum hemorrhage, were in active labor (defined as having a cervix diameter of greater than 3 cm), or had suspected chorioamnionitis.

All of the women received routine care. A swab for fetal fibronectin testing was obtained according to usual protocol; per institutional procedure at the time, the swab was kept for 2 hours and analyzed only if symptoms of labor were still equivocal.

A cervical swab was obtained for ph IGFBP-1 measurement with the Actim Partus test. Patients who were ineligible for a fetal fibronectin test because of a recent vaginal examination or intercourse still had this test. All of these swabs were analyzed by a study registered nurse who was blinded to the patient's clinical course.

The women were 29 years old, on average. The mean gestational age was 29.8 weeks. Forty-three percent were nulliparous, and 16% had previously experienced a preterm birth. Three-fourths had a cervical dilation on admission of 0-1 cm.

Swabs were processed for ph IGFBP-1 in all 349 women, but for fetal fibronectin in only 288 of them. In other words, 17% of the women did not have the latter test run either because they were ineligible because of recent vaginal examination or intercourse or because labor was no longer equivocal after the 2-hour wait.

Overall, 26% of the ph IGFBP-1 test results were positive (had a value of at least 10 mcg/L), and 8% of the fetal fibronectin test results were positive (had a value of at least 50 ng/mL).

Only 16% of the women were delivered preterm (before 37 weeks' gestation). “This just goes to show that the majority of patients who present with preterm labor actually will not deliver preterm,” Dr. Cooper commented.

The ph IGFBP-1 test and the fetal fibronectin test had similarly good negative predictive values for preterm delivery (0.86 and 0.88).

The positive predictive value was poor for both, although somewhat more so for ph IGFBP-1 (0.22 and 0.54).

The ph IGFBP-1 test and the fetal fibronectin test also both had poor sensitivity (39% and 33%), while specificity was marginally poorer for the former test (74% and 95%).

The investigators also assessed the performance of the two tests combined. “There were times when they agreed and times when they didn't agree, but it didn't seem to be that combining them together improved your predictability,” she said.

Recent data suggest that predictability may improve when a biochemical marker is combined with cervical length on ultrasound, noted Dr. Cooper.

“The problem is, we are looking for a rapid bedside test for people in rural areas who don't have resources,” she commented. “So if we start putting cervical length into the mix, then it takes away the primary objective of how do we help people who are living in rural areas that are rural enough to have to make decisions about clinical transfer.”

Major Finding: The negative predictive values for preterm delivery were similarly high for ph IGFBP-1 and fetal fibronectin; the positive predictive values were poor for both.

Data Source: A prospective cohort study among 349 women with symptoms of preterm labor.

Disclosures: Dr. Cooper reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – The phosphorylated insulinlike growth factor binding protein–1 test may edge out the fetal fibronectin test when it comes to predicting preterm delivery, a study has shown.

In the prospective cohort study among 349 women with symptoms of preterm labor, the two tests had similarly good negative predictive values, 0.86 and 0.88, researchers reported at the meeting. Both had poor sensitivity and positive predictive values.

However, the phosphorylated insulinlike growth factor binding protein–1 (ph IGFBP-1) test (marketed outside the United States as the Actim Partus test) costs about one-fourth as much as the fetal fibronectin test. Also, the former is a simple dipstick test that can be run at the bedside, and it differs in not being affected by recent intercourse or vaginal examinations.

The Actim Partus test is not currently available in the United States. “The timeline for its clearance and availability in the United States is … not yet known,” according to a spokeswoman for Medix Biochemica, Kauniainen, Finland.

“The Actim Partus compares favorably to fetal fibronectin for the ability to rule out preterm labor,” said lead investigator Dr. Stephanie Cooper, program director of maternal-fetal medicine at the University of Calgary (Alta.). “Given the benefit of reduced cost, efficiency, and ability to use it in a broad clinical scenario, institutions should consider using the newer test, the Partus test, until better tools are available.”

Her institution has not yet switched to the new test. “But what I will say is these results definitely make me do fetal fibronectin less,” she commented. “I don't think Partus is a good test, I don't think fibronectin is a good test. … I'm hoping that there's going to be a better test.”

Fetal fibronectin is generally regarded as the gold standard for predicting preterm delivery, according to Dr. Cooper.

However, “it is not a perfect test. In fact, maybe it's more like the bronze standard,” she commented. Its limitations include a poor positive predictive value; false-positivity in women who have recently had a vaginal exam or intercourse; cost; and, usually, the need for a laboratory for analysis.

“Ph IGFBP-1 is released by the cervix following disruption of the choriodecidual barrier, which we believe occurs with the onset of labor,” she explained. It has shown promise for overcoming some of the limitations of the fetal fibronectin test.

The researchers enrolled in the study 349 women who had symptoms of labor preterm (between 24 and 34 weeks' gestation) and no contraindications to vaginal examination.

Women were ineligible if they had ruptured membranes, had antepartum hemorrhage, were in active labor (defined as having a cervix diameter of greater than 3 cm), or had suspected chorioamnionitis.

All of the women received routine care. A swab for fetal fibronectin testing was obtained according to usual protocol; per institutional procedure at the time, the swab was kept for 2 hours and analyzed only if symptoms of labor were still equivocal.

A cervical swab was obtained for ph IGFBP-1 measurement with the Actim Partus test. Patients who were ineligible for a fetal fibronectin test because of a recent vaginal examination or intercourse still had this test. All of these swabs were analyzed by a study registered nurse who was blinded to the patient's clinical course.

The women were 29 years old, on average. The mean gestational age was 29.8 weeks. Forty-three percent were nulliparous, and 16% had previously experienced a preterm birth. Three-fourths had a cervical dilation on admission of 0-1 cm.

Swabs were processed for ph IGFBP-1 in all 349 women, but for fetal fibronectin in only 288 of them. In other words, 17% of the women did not have the latter test run either because they were ineligible because of recent vaginal examination or intercourse or because labor was no longer equivocal after the 2-hour wait.

Overall, 26% of the ph IGFBP-1 test results were positive (had a value of at least 10 mcg/L), and 8% of the fetal fibronectin test results were positive (had a value of at least 50 ng/mL).

Only 16% of the women were delivered preterm (before 37 weeks' gestation). “This just goes to show that the majority of patients who present with preterm labor actually will not deliver preterm,” Dr. Cooper commented.

The ph IGFBP-1 test and the fetal fibronectin test had similarly good negative predictive values for preterm delivery (0.86 and 0.88).

The positive predictive value was poor for both, although somewhat more so for ph IGFBP-1 (0.22 and 0.54).

The ph IGFBP-1 test and the fetal fibronectin test also both had poor sensitivity (39% and 33%), while specificity was marginally poorer for the former test (74% and 95%).

The investigators also assessed the performance of the two tests combined. “There were times when they agreed and times when they didn't agree, but it didn't seem to be that combining them together improved your predictability,” she said.

Recent data suggest that predictability may improve when a biochemical marker is combined with cervical length on ultrasound, noted Dr. Cooper.

“The problem is, we are looking for a rapid bedside test for people in rural areas who don't have resources,” she commented. “So if we start putting cervical length into the mix, then it takes away the primary objective of how do we help people who are living in rural areas that are rural enough to have to make decisions about clinical transfer.”

Major Finding: The negative predictive values for preterm delivery were similarly high for ph IGFBP-1 and fetal fibronectin; the positive predictive values were poor for both.

Data Source: A prospective cohort study among 349 women with symptoms of preterm labor.

Disclosures: Dr. Cooper reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – The phosphorylated insulinlike growth factor binding protein–1 test may edge out the fetal fibronectin test when it comes to predicting preterm delivery, a study has shown.

In the prospective cohort study among 349 women with symptoms of preterm labor, the two tests had similarly good negative predictive values, 0.86 and 0.88, researchers reported at the meeting. Both had poor sensitivity and positive predictive values.

However, the phosphorylated insulinlike growth factor binding protein–1 (ph IGFBP-1) test (marketed outside the United States as the Actim Partus test) costs about one-fourth as much as the fetal fibronectin test. Also, the former is a simple dipstick test that can be run at the bedside, and it differs in not being affected by recent intercourse or vaginal examinations.

The Actim Partus test is not currently available in the United States. “The timeline for its clearance and availability in the United States is … not yet known,” according to a spokeswoman for Medix Biochemica, Kauniainen, Finland.

“The Actim Partus compares favorably to fetal fibronectin for the ability to rule out preterm labor,” said lead investigator Dr. Stephanie Cooper, program director of maternal-fetal medicine at the University of Calgary (Alta.). “Given the benefit of reduced cost, efficiency, and ability to use it in a broad clinical scenario, institutions should consider using the newer test, the Partus test, until better tools are available.”

Her institution has not yet switched to the new test. “But what I will say is these results definitely make me do fetal fibronectin less,” she commented. “I don't think Partus is a good test, I don't think fibronectin is a good test. … I'm hoping that there's going to be a better test.”

Fetal fibronectin is generally regarded as the gold standard for predicting preterm delivery, according to Dr. Cooper.

However, “it is not a perfect test. In fact, maybe it's more like the bronze standard,” she commented. Its limitations include a poor positive predictive value; false-positivity in women who have recently had a vaginal exam or intercourse; cost; and, usually, the need for a laboratory for analysis.

“Ph IGFBP-1 is released by the cervix following disruption of the choriodecidual barrier, which we believe occurs with the onset of labor,” she explained. It has shown promise for overcoming some of the limitations of the fetal fibronectin test.

The researchers enrolled in the study 349 women who had symptoms of labor preterm (between 24 and 34 weeks' gestation) and no contraindications to vaginal examination.

Women were ineligible if they had ruptured membranes, had antepartum hemorrhage, were in active labor (defined as having a cervix diameter of greater than 3 cm), or had suspected chorioamnionitis.

All of the women received routine care. A swab for fetal fibronectin testing was obtained according to usual protocol; per institutional procedure at the time, the swab was kept for 2 hours and analyzed only if symptoms of labor were still equivocal.

A cervical swab was obtained for ph IGFBP-1 measurement with the Actim Partus test. Patients who were ineligible for a fetal fibronectin test because of a recent vaginal examination or intercourse still had this test. All of these swabs were analyzed by a study registered nurse who was blinded to the patient's clinical course.

The women were 29 years old, on average. The mean gestational age was 29.8 weeks. Forty-three percent were nulliparous, and 16% had previously experienced a preterm birth. Three-fourths had a cervical dilation on admission of 0-1 cm.

Swabs were processed for ph IGFBP-1 in all 349 women, but for fetal fibronectin in only 288 of them. In other words, 17% of the women did not have the latter test run either because they were ineligible because of recent vaginal examination or intercourse or because labor was no longer equivocal after the 2-hour wait.

Overall, 26% of the ph IGFBP-1 test results were positive (had a value of at least 10 mcg/L), and 8% of the fetal fibronectin test results were positive (had a value of at least 50 ng/mL).

Only 16% of the women were delivered preterm (before 37 weeks' gestation). “This just goes to show that the majority of patients who present with preterm labor actually will not deliver preterm,” Dr. Cooper commented.

The ph IGFBP-1 test and the fetal fibronectin test had similarly good negative predictive values for preterm delivery (0.86 and 0.88).

The positive predictive value was poor for both, although somewhat more so for ph IGFBP-1 (0.22 and 0.54).

The ph IGFBP-1 test and the fetal fibronectin test also both had poor sensitivity (39% and 33%), while specificity was marginally poorer for the former test (74% and 95%).

The investigators also assessed the performance of the two tests combined. “There were times when they agreed and times when they didn't agree, but it didn't seem to be that combining them together improved your predictability,” she said.

Recent data suggest that predictability may improve when a biochemical marker is combined with cervical length on ultrasound, noted Dr. Cooper.

“The problem is, we are looking for a rapid bedside test for people in rural areas who don't have resources,” she commented. “So if we start putting cervical length into the mix, then it takes away the primary objective of how do we help people who are living in rural areas that are rural enough to have to make decisions about clinical transfer.”

Major Finding: Pregnancy-related hospitalizations for stroke in the United States increased by 54% from 1994-1995 to 2006-2007.

Data Source: A review of ICD-9 code data from 64,023,525 women nationwide.

Disclosures: Dr. Kuklina and her associates said they had no relevant financial disclosures.

The rate of any type of pregnancy-related hospitalization for stroke in the United States increased from approximately 4,000 in 1994-1995 to about 6,000 in 2006-2007, based on data from a nationwide sample of more than 64 million pregnant women.

This 54% increase can be explained largely by postpartum hospitalizations in women with heart disease or hypertensive disorders, said Dr. Elena V. Kuklina and her associates at the Centers for Disease Control and Prevention in Atlanta.

The researchers compared ICD-9 code data from 1994 to 1995 with data from 2006 to 2007. Types of stroke included cerebral venous thrombosis, hemorrhagic, ischemic, subarachnoid, transient ischemic attack, and unspecified (Stroke 2011 J [doi:10.1161/strokeaha.110. 610592]). Overall, hypertensive disorders were present in 11%, 23%, and 28% of prenatal, delivery, and postpartum hospitalizations, respectively, in 1994-1995, and these numbers increased to 17%, 29%, and 41% in 2006-2007. Only the increase in postpartum hospitalizations for stroke was statistically significant.

Heart disease was a complication in pregnancy-related hospitalizations for stroke in 16% of prenatal hospitalizations, 8% of delivery hospitalizations, and 9% of postpartum hospitalizations in 1994-1995, whereas that was the case in 16%, 8%, and 12% of the hospitalizations, respectively, in 2006-2007.

The rate of any stroke per 1,000 deliveries increased significantly for prenatal hospitalizations and postpartum hospitalizations between the two time periods (from 0.15 to 0.22 and from 0.12 to 0.22, respectively). However, the rate of any stroke during delivery hospitalizations remained unchanged at 0.27.

After adjustiment for confounding variables, patients who were hospitalized with hypertensive disorders during pregnancy, during delivery, and post partum were 1.8, 5.6, and 3.5 times more likely, respectively, to have indications of stroke, compared with patients without hypertensive disorders, the researchers noted.

In addition, patients who were hospitalized with heart disease during the prenatal period and the delivery period were, respectively, 9.4 times as likely and 5.4 times as likely to have indications of stroke.

The current recommendations from the American Heart Association and the American Stroke Association for managing pregnant women with a history of noncardioembolic stroke or at risk of cardioembolic stroke include treatment with anticoagulant therapy in the form of unfractionated heparin or low-molecular-weight heparin until week 13, followed by low dose aspirin for the rest of the pregnancy (Stroke 2011;42:227-76).

Major Finding: Pregnancy-related hospitalizations for stroke in the United States increased by 54% from 1994-1995 to 2006-2007.

Data Source: A review of ICD-9 code data from 64,023,525 women nationwide.

Disclosures: Dr. Kuklina and her associates said they had no relevant financial disclosures.

The rate of any type of pregnancy-related hospitalization for stroke in the United States increased from approximately 4,000 in 1994-1995 to about 6,000 in 2006-2007, based on data from a nationwide sample of more than 64 million pregnant women.

This 54% increase can be explained largely by postpartum hospitalizations in women with heart disease or hypertensive disorders, said Dr. Elena V. Kuklina and her associates at the Centers for Disease Control and Prevention in Atlanta.

The researchers compared ICD-9 code data from 1994 to 1995 with data from 2006 to 2007. Types of stroke included cerebral venous thrombosis, hemorrhagic, ischemic, subarachnoid, transient ischemic attack, and unspecified (Stroke 2011 J [doi:10.1161/strokeaha.110. 610592]). Overall, hypertensive disorders were present in 11%, 23%, and 28% of prenatal, delivery, and postpartum hospitalizations, respectively, in 1994-1995, and these numbers increased to 17%, 29%, and 41% in 2006-2007. Only the increase in postpartum hospitalizations for stroke was statistically significant.

Heart disease was a complication in pregnancy-related hospitalizations for stroke in 16% of prenatal hospitalizations, 8% of delivery hospitalizations, and 9% of postpartum hospitalizations in 1994-1995, whereas that was the case in 16%, 8%, and 12% of the hospitalizations, respectively, in 2006-2007.

The rate of any stroke per 1,000 deliveries increased significantly for prenatal hospitalizations and postpartum hospitalizations between the two time periods (from 0.15 to 0.22 and from 0.12 to 0.22, respectively). However, the rate of any stroke during delivery hospitalizations remained unchanged at 0.27.

After adjustiment for confounding variables, patients who were hospitalized with hypertensive disorders during pregnancy, during delivery, and post partum were 1.8, 5.6, and 3.5 times more likely, respectively, to have indications of stroke, compared with patients without hypertensive disorders, the researchers noted.

In addition, patients who were hospitalized with heart disease during the prenatal period and the delivery period were, respectively, 9.4 times as likely and 5.4 times as likely to have indications of stroke.

The current recommendations from the American Heart Association and the American Stroke Association for managing pregnant women with a history of noncardioembolic stroke or at risk of cardioembolic stroke include treatment with anticoagulant therapy in the form of unfractionated heparin or low-molecular-weight heparin until week 13, followed by low dose aspirin for the rest of the pregnancy (Stroke 2011;42:227-76).

Major Finding: Pregnancy-related hospitalizations for stroke in the United States increased by 54% from 1994-1995 to 2006-2007.

Data Source: A review of ICD-9 code data from 64,023,525 women nationwide.

Disclosures: Dr. Kuklina and her associates said they had no relevant financial disclosures.

The rate of any type of pregnancy-related hospitalization for stroke in the United States increased from approximately 4,000 in 1994-1995 to about 6,000 in 2006-2007, based on data from a nationwide sample of more than 64 million pregnant women.

This 54% increase can be explained largely by postpartum hospitalizations in women with heart disease or hypertensive disorders, said Dr. Elena V. Kuklina and her associates at the Centers for Disease Control and Prevention in Atlanta.

The researchers compared ICD-9 code data from 1994 to 1995 with data from 2006 to 2007. Types of stroke included cerebral venous thrombosis, hemorrhagic, ischemic, subarachnoid, transient ischemic attack, and unspecified (Stroke 2011 J [doi:10.1161/strokeaha.110. 610592]). Overall, hypertensive disorders were present in 11%, 23%, and 28% of prenatal, delivery, and postpartum hospitalizations, respectively, in 1994-1995, and these numbers increased to 17%, 29%, and 41% in 2006-2007. Only the increase in postpartum hospitalizations for stroke was statistically significant.

Heart disease was a complication in pregnancy-related hospitalizations for stroke in 16% of prenatal hospitalizations, 8% of delivery hospitalizations, and 9% of postpartum hospitalizations in 1994-1995, whereas that was the case in 16%, 8%, and 12% of the hospitalizations, respectively, in 2006-2007.

The rate of any stroke per 1,000 deliveries increased significantly for prenatal hospitalizations and postpartum hospitalizations between the two time periods (from 0.15 to 0.22 and from 0.12 to 0.22, respectively). However, the rate of any stroke during delivery hospitalizations remained unchanged at 0.27.

After adjustiment for confounding variables, patients who were hospitalized with hypertensive disorders during pregnancy, during delivery, and post partum were 1.8, 5.6, and 3.5 times more likely, respectively, to have indications of stroke, compared with patients without hypertensive disorders, the researchers noted.

In addition, patients who were hospitalized with heart disease during the prenatal period and the delivery period were, respectively, 9.4 times as likely and 5.4 times as likely to have indications of stroke.

The current recommendations from the American Heart Association and the American Stroke Association for managing pregnant women with a history of noncardioembolic stroke or at risk of cardioembolic stroke include treatment with anticoagulant therapy in the form of unfractionated heparin or low-molecular-weight heparin until week 13, followed by low dose aspirin for the rest of the pregnancy (Stroke 2011;42:227-76).

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogs,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogs, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15).

Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007;24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation,” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators of a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord/maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogs, or oral hypoglycemics could affect “in-utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about IGF-I receptor affinity and increased mitogenic potency of some of the insulin analogues.

“Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

Dr. Rosenn reported that he had no relevant financial disclosures.

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogs,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogs, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15).

Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007;24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation,” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators of a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord/maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogs, or oral hypoglycemics could affect “in-utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about IGF-I receptor affinity and increased mitogenic potency of some of the insulin analogues.

“Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

Dr. Rosenn reported that he had no relevant financial disclosures.

WASHINGTON – Insulins and oral hypoglycemics used during pregnancy can theoretically cause harm to the fetus, but evidence of harm is lacking, said Dr. Barak M. Rosenn.

“Is there any evidence that pharmacologic agents used in the treatment of gestational diabetes can indeed and do indeed cause harm? Not really,” said Dr. Rosenn, director of the division of obstetrics and maternal-fetal medicine at St. Luke's-Roosevelt Hospital in New York.

On the other hand, there have been “no long-term follow-up studies of infants whose mothers were treated with metformin, glyburide, or any of the insulin analogs,” he noted, and past experience with thalidomide has shown that “what may seem safe in the present may prove to be unsafe in the future.”

“Like anything in medicine, we have to be aware of potential risks and weigh the potential risks and benefits,” he said at the meeting. “We can't ignore the fact that diabetes in pregnancy has to be treated.”

Transplacental passage of insulin, insulin analogs, and metformin has indeed been demonstrated, he said.

In 1990, for instance, investigators reported that antibody-bound animal insulin was transferred from mother to fetus, and that the extent of transfer correlated with the maternal concentration of anti-insulin antibody (N. Engl. J. Med. 1990;323:309-15).

Another study published in 2007 reported a similar insulin antibody response – and placental passage – in women with gestational diabetes mellitus (GDM) who were receiving human insulin (Diabetes Care 1997;20:1172-5).

In vitro studies on term placentas have demonstrated the transfer of lispro, and aspart has been detected in the cord blood at delivery (Diabet. Med. 2007;24:1129-35). A transplacental passage study of glargine “again showed small amounts crossing into the fetal circulation,” but with higher doses, Dr. Rosenn said (Diabetes Care 2010;33:29-33). hWe don't know what this small amount [of transfer] means for the fetus,” he noted.

In vitro studies have shown metformin to cross the placenta “almost freely,” and clinical studies measuring metformin concentrations in the maternal and cord blood have shown at least comparable maternal-fetal levels of the antihyperglycemic agent. “There's some suggestion that [metformin concentrations] may even be higher in [the fetus],” he said. “But again, the question is, 'What does it do to the fetus apart from the fact that it controls glucose in the mother?'”

With glyburide, the degree of transplacental passage is less clear. Investigators of a recent Obstetric-Fetal Pharmacology Research Unit Network study on glyburide in 40 women with GDM reported that the average ratio of umbilical cord/maternal plasma glyburide concentration was 0.7 at the time of delivery (Clin. Pharmacol. Ther. 2009;85:607-14).

“I do have an argument with the validity of this declaration … because it's pretty obvious that, based on concentrations in the mothers … it [had been] a long time after the last dose [in most mothers],” he said.

The fetal concentration “may be low, but it's not normal,” noted Dr. Rosenn, also professor of obstetrics and gynecology at Columbia University, New York.

Theoretically, it's possible that small quantities of insulin, insulin analogs, or oral hypoglycemics could affect “in-utero fetal programming with respect to sensitivity to insulin or insulin resistance” or could cause undetected fetal hypoglycemia in utero,” he said.

Concern has been expressed, moreover, about IGF-I receptor affinity and increased mitogenic potency of some of the insulin analogues.

“Concern has been raised with respect to the mom, but if indeed these cross the placenta, we have [to consider] the fetus as well,” Dr. Rosenn said.

Dr. Rosenn reported that he had no relevant financial disclosures.