Jeff Evans

WASHINGTON – Which comes first, diabetes or depression?

The data on this temporal relationship are mixed. While findings from previous studies suggest that depression precedes diabetes, findings from another investigation, presented at the annual scientific sessions of the American Diabetes Association, propose that no time correlation exists between the two diagnoses.

This chicken-or-egg question is important because depression has a reported prevalence ranging from 11% to 33% in patients with diabetes, which is twice as high as it is in people without diabetes, said Dr. Lawrence S. Phillips, professor of medicine in the division of endocrinology and metabolism at Emory University, Atlanta.

Dr. Phillips and his colleagues conducted a cross-sectional study of 573 people (about half were white and half were African American) who said that they did not have diabetes. Each person received a 75-g oral glucose tolerance test after an 8-hour overnight fast, and screening for depression with a well-validated tool, the Patient Health Questionnaire.

Normal glucose tolerance (NGT) occurred in 65% of the participants while 15% had impaired fasting glucose (IFG), 8% had impaired glucose tolerance (IGT), 8% had both IFG and IGT, and 4% had diabetes. Some participants had received (11%) or were currently receiving (12%) treatment for depression.

PHQ scores rose in a statistically significant trend from being low among those who never underwent treatment for depression to being higher in people who received depression treatment in the past and highest in individuals who were currently receiving depression treatment.

But there was no relationship between the different categories of glucose tolerance and PHQ score, the prevalence of any depressive syndrome or major depressive disorder, or the severity of depression, Dr. Phillips said.

In multivariate analyses, higher body mass index and current receipt of depression treatment significantly increased the risk of having any depressive syndrome, but this risk was not increased within any category of glucose tolerance.

One audience member asked Dr. Phillips how he viewed the results of his study in light of the fact that a poster presented at last year's ADA meeting found that patients with IGT in the Diabetes Prevention Program had a significantly increased risk for depression, suggesting depression may have preceded IGT.

“It's certainly possible that among people who are depressed, there are neuroendocrine changes that lead to diabetes. There's certainly room in human biology for both processes,” Dr. Phillips said.

But he argued that the situation in which depression precedes the development of diabetes is unlikely given the lack of an association between depression and unrecognized IGT in his study and the fact that patients in the Diabetes Prevention Program were told that they had IGT and were at risk for diabetes, which could possibly have had a negative psychosocial effect.

Firm conclusions favoring either side of the issue, however, may have to wait for research into the dynamics of neurohormonal changes, which are believed to underlie some of the association between depression and the development of diabetes, said Dr. Sherita Hill Golden of the division of endocrinology and metabolism at Johns Hopkins University, Baltimore.

Melancholic depression is known to increase the activation of the hypothalamic pituitary adrenal (HPA) axis, which leads to a simultaneous activation of the sympathetic nervous system, Dr. Golden said.

In the tightly regulated feedback loop of the HPA axis, the hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to release adrenocorticotropin hormone (ACTH), which stimulates the adrenal gland to release cortisol. Cortisol levels then in turn regulate the production and release of CRH.

There is evidence to suggest that subclinical hypercortisolism, defined as having two of three abnormalities in HPA axis function (increased 24-hour urine free cortisol, failure of the dexamethasone suppression test, and decreased levels of ACTH), may contribute to the development of type 2 diabetes, Dr. Golden said.

One study of 12 patients with adrenal incidentalomas and subclinical hypercortisolism found that such patients had a higher prevalence of insulin resistance, impaired glucose tolerance, and type 2 diabetes, as well as greater central adiposity, than did 29 patients with a nonfunctioning adrenal incidentaloma and no subclinical hypercortisolism (J. Clin. Endocrinol. Metab. 2002;87:998–1003).

Dr. Golden's own research has centered on determining which measures of neuroendocrine activity provide the most reliable results, and understanding how that activity correlates with metabolic parameters. Preliminary results of an extensive 3-day series of tests in 15 healthy African American women have indicated that static measures of HPA axis activity, such as salivary cortisol sampling, do not correlate well with more dynamic measurements, such as 24-hour urine-free cortisol levels. Other analyses in the patient group suggested that CT scan measurements of adrenal gland volume and the results of dexamethasone suppression testing are correlated strongly with body mass index, high-density lipoprotein cholesterol, and systolic blood pressure.

The results of studies measuring the effect of neuroendocrine changes on metabolic parameters are beginning to suggest that “modification of the neurohormonal response may provide a novel approach to the primary prevention of type 2 diabetes,” Dr. Golden said.

WASHINGTON – Which comes first, diabetes or depression?

The data on this temporal relationship are mixed. While findings from previous studies suggest that depression precedes diabetes, findings from another investigation, presented at the annual scientific sessions of the American Diabetes Association, propose that no time correlation exists between the two diagnoses.

This chicken-or-egg question is important because depression has a reported prevalence ranging from 11% to 33% in patients with diabetes, which is twice as high as it is in people without diabetes, said Dr. Lawrence S. Phillips, professor of medicine in the division of endocrinology and metabolism at Emory University, Atlanta.

Dr. Phillips and his colleagues conducted a cross-sectional study of 573 people (about half were white and half were African American) who said that they did not have diabetes. Each person received a 75-g oral glucose tolerance test after an 8-hour overnight fast, and screening for depression with a well-validated tool, the Patient Health Questionnaire.

Normal glucose tolerance (NGT) occurred in 65% of the participants while 15% had impaired fasting glucose (IFG), 8% had impaired glucose tolerance (IGT), 8% had both IFG and IGT, and 4% had diabetes. Some participants had received (11%) or were currently receiving (12%) treatment for depression.

PHQ scores rose in a statistically significant trend from being low among those who never underwent treatment for depression to being higher in people who received depression treatment in the past and highest in individuals who were currently receiving depression treatment.

But there was no relationship between the different categories of glucose tolerance and PHQ score, the prevalence of any depressive syndrome or major depressive disorder, or the severity of depression, Dr. Phillips said.

In multivariate analyses, higher body mass index and current receipt of depression treatment significantly increased the risk of having any depressive syndrome, but this risk was not increased within any category of glucose tolerance.

One audience member asked Dr. Phillips how he viewed the results of his study in light of the fact that a poster presented at last year's ADA meeting found that patients with IGT in the Diabetes Prevention Program had a significantly increased risk for depression, suggesting depression may have preceded IGT.

“It's certainly possible that among people who are depressed, there are neuroendocrine changes that lead to diabetes. There's certainly room in human biology for both processes,” Dr. Phillips said.

But he argued that the situation in which depression precedes the development of diabetes is unlikely given the lack of an association between depression and unrecognized IGT in his study and the fact that patients in the Diabetes Prevention Program were told that they had IGT and were at risk for diabetes, which could possibly have had a negative psychosocial effect.

Firm conclusions favoring either side of the issue, however, may have to wait for research into the dynamics of neurohormonal changes, which are believed to underlie some of the association between depression and the development of diabetes, said Dr. Sherita Hill Golden of the division of endocrinology and metabolism at Johns Hopkins University, Baltimore.

Melancholic depression is known to increase the activation of the hypothalamic pituitary adrenal (HPA) axis, which leads to a simultaneous activation of the sympathetic nervous system, Dr. Golden said.

In the tightly regulated feedback loop of the HPA axis, the hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to release adrenocorticotropin hormone (ACTH), which stimulates the adrenal gland to release cortisol. Cortisol levels then in turn regulate the production and release of CRH.

There is evidence to suggest that subclinical hypercortisolism, defined as having two of three abnormalities in HPA axis function (increased 24-hour urine free cortisol, failure of the dexamethasone suppression test, and decreased levels of ACTH), may contribute to the development of type 2 diabetes, Dr. Golden said.

One study of 12 patients with adrenal incidentalomas and subclinical hypercortisolism found that such patients had a higher prevalence of insulin resistance, impaired glucose tolerance, and type 2 diabetes, as well as greater central adiposity, than did 29 patients with a nonfunctioning adrenal incidentaloma and no subclinical hypercortisolism (J. Clin. Endocrinol. Metab. 2002;87:998–1003).

Dr. Golden's own research has centered on determining which measures of neuroendocrine activity provide the most reliable results, and understanding how that activity correlates with metabolic parameters. Preliminary results of an extensive 3-day series of tests in 15 healthy African American women have indicated that static measures of HPA axis activity, such as salivary cortisol sampling, do not correlate well with more dynamic measurements, such as 24-hour urine-free cortisol levels. Other analyses in the patient group suggested that CT scan measurements of adrenal gland volume and the results of dexamethasone suppression testing are correlated strongly with body mass index, high-density lipoprotein cholesterol, and systolic blood pressure.

The results of studies measuring the effect of neuroendocrine changes on metabolic parameters are beginning to suggest that “modification of the neurohormonal response may provide a novel approach to the primary prevention of type 2 diabetes,” Dr. Golden said.

WASHINGTON – Which comes first, diabetes or depression?

The data on this temporal relationship are mixed. While findings from previous studies suggest that depression precedes diabetes, findings from another investigation, presented at the annual scientific sessions of the American Diabetes Association, propose that no time correlation exists between the two diagnoses.

This chicken-or-egg question is important because depression has a reported prevalence ranging from 11% to 33% in patients with diabetes, which is twice as high as it is in people without diabetes, said Dr. Lawrence S. Phillips, professor of medicine in the division of endocrinology and metabolism at Emory University, Atlanta.

Dr. Phillips and his colleagues conducted a cross-sectional study of 573 people (about half were white and half were African American) who said that they did not have diabetes. Each person received a 75-g oral glucose tolerance test after an 8-hour overnight fast, and screening for depression with a well-validated tool, the Patient Health Questionnaire.

Normal glucose tolerance (NGT) occurred in 65% of the participants while 15% had impaired fasting glucose (IFG), 8% had impaired glucose tolerance (IGT), 8% had both IFG and IGT, and 4% had diabetes. Some participants had received (11%) or were currently receiving (12%) treatment for depression.

PHQ scores rose in a statistically significant trend from being low among those who never underwent treatment for depression to being higher in people who received depression treatment in the past and highest in individuals who were currently receiving depression treatment.

But there was no relationship between the different categories of glucose tolerance and PHQ score, the prevalence of any depressive syndrome or major depressive disorder, or the severity of depression, Dr. Phillips said.

In multivariate analyses, higher body mass index and current receipt of depression treatment significantly increased the risk of having any depressive syndrome, but this risk was not increased within any category of glucose tolerance.

One audience member asked Dr. Phillips how he viewed the results of his study in light of the fact that a poster presented at last year's ADA meeting found that patients with IGT in the Diabetes Prevention Program had a significantly increased risk for depression, suggesting depression may have preceded IGT.

“It's certainly possible that among people who are depressed, there are neuroendocrine changes that lead to diabetes. There's certainly room in human biology for both processes,” Dr. Phillips said.

But he argued that the situation in which depression precedes the development of diabetes is unlikely given the lack of an association between depression and unrecognized IGT in his study and the fact that patients in the Diabetes Prevention Program were told that they had IGT and were at risk for diabetes, which could possibly have had a negative psychosocial effect.

Firm conclusions favoring either side of the issue, however, may have to wait for research into the dynamics of neurohormonal changes, which are believed to underlie some of the association between depression and the development of diabetes, said Dr. Sherita Hill Golden of the division of endocrinology and metabolism at Johns Hopkins University, Baltimore.

Melancholic depression is known to increase the activation of the hypothalamic pituitary adrenal (HPA) axis, which leads to a simultaneous activation of the sympathetic nervous system, Dr. Golden said.

In the tightly regulated feedback loop of the HPA axis, the hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to release adrenocorticotropin hormone (ACTH), which stimulates the adrenal gland to release cortisol. Cortisol levels then in turn regulate the production and release of CRH.

There is evidence to suggest that subclinical hypercortisolism, defined as having two of three abnormalities in HPA axis function (increased 24-hour urine free cortisol, failure of the dexamethasone suppression test, and decreased levels of ACTH), may contribute to the development of type 2 diabetes, Dr. Golden said.

One study of 12 patients with adrenal incidentalomas and subclinical hypercortisolism found that such patients had a higher prevalence of insulin resistance, impaired glucose tolerance, and type 2 diabetes, as well as greater central adiposity, than did 29 patients with a nonfunctioning adrenal incidentaloma and no subclinical hypercortisolism (J. Clin. Endocrinol. Metab. 2002;87:998–1003).

Dr. Golden's own research has centered on determining which measures of neuroendocrine activity provide the most reliable results, and understanding how that activity correlates with metabolic parameters. Preliminary results of an extensive 3-day series of tests in 15 healthy African American women have indicated that static measures of HPA axis activity, such as salivary cortisol sampling, do not correlate well with more dynamic measurements, such as 24-hour urine-free cortisol levels. Other analyses in the patient group suggested that CT scan measurements of adrenal gland volume and the results of dexamethasone suppression testing are correlated strongly with body mass index, high-density lipoprotein cholesterol, and systolic blood pressure.

The results of studies measuring the effect of neuroendocrine changes on metabolic parameters are beginning to suggest that “modification of the neurohormonal response may provide a novel approach to the primary prevention of type 2 diabetes,” Dr. Golden said.

WASHINGTON — Analysis of skin punch biopsy specimens may help predict diabetic neuropathy in at-risk patients, diagnose the condition earlier, and assess treatment response, Dr. Michael Polydefkis said at the annual scientific sessions of the American Diabetes Association.

Skin punch biopsy specimens contain small unmyelinated nerve fibers that are damaged in early diabetes. Normative data have shown that the degree of involvement is related to the degree of glucose dysmetabolism, said Dr. Polydefkis, codirector of the cutaneous nerve laboratory at Johns Hopkins University, Baltimore.

Analysis of skin biopsy specimens can help exclude other potential causes of painful feet such as radiculopathy, Morton's neuroma, tarsal tunnel syndrome, and intrinsic foot disease, he said.

A 3-mm diameter, circular skin punch biopsy specimen (about half the size of a pencil eraser) is sliced into about 60 sections, 4 of which are randomly selected for analysis to reduce sample bias since there may be differences in nerve density in different parts of the specimen. Biopsies should be taken at the ankle or other distal sites in patients with early neuropathic symptoms but at the thigh or other proximal sites in those with advanced neuropathy, he said.

In a study of 73 patients with an unknown cause of peripheral neuropathy, Dr. Polydefkis and his associates found that epidermal nerve fiber density (ENFD) in skin punch biopsy specimens was a good marker of early neuropathy. Of the 73 patients, 25 were diagnosed with impaired glucose tolerance (IGT) and 16 had diabetes.

The ENFD in biopsy specimens of patients with diabetes or IGT was significantly reduced, compared with healthy control patients. In specimens from the distal leg but not the distal or proximal thigh, diabetic patients had significantly lower ENFD than did patients with IGT. Yet nerve conduction studies yielded normal results on average in both groups.

Dr. Polydefkis and his associates concluded that the measurement of ENFD in skin punch biopsies is a more sensitive marker for detecting neuropathy early than are nerve conduction studies that test the function of large myelinated nerve fibers (Neurology 2003;60:108–11).

At the end of an average follow-up of 4.4 years, repeat testing in 29 patients showed that decline in ENFD was greatest in patients with diabetes, followed by patients with IGT and patients with idiopathic neuropathy. ENFD was essentially stable in 10 healthy control patients. “This longitudinal data provide some of the best evidence that the association between IGT and neuropathy is, in fact, causal,” Dr. Polydefkis said.

Information on nerve morphology also can be extracted from skin punch biopsy specimens. In one study, investigators performed nerve conduction studies, quantitative sensory testing, and skin punch biopsies in the proximal thigh and distal leg at baseline and after a mean of 19 months of follow-up in 15 patients with foot pain but few or no symptoms of neuropathy (6 with diabetes, 1 with AIDS, 1 with paclitaxel toxicity, 7 with an idiopathic nature) and 15 age-matched, healthy control patients.

At baseline, patients had significantly lower ENFD in the distal leg than did controls. At follow-up, the ENFD had declined in both biopsy locations but only by a significant amount in the distal leg, compared with the controls (Neurology 2003;61:631–6).

The results of that study provide “evidence that the skin biopsy can be used to predict development of neuropathy,” Dr. Polydefkis said.

Clinically meaningful changes in ENFD are on the order of a loss of 2–3 nerve fibers per millimeter. Diabetic patients who present with painful peripheral neuropathy appear to have ENFD losses in the range of 1 fiber/mm per year, while losses for those with established diabetes and peripheral neuropathy may be slightly higher, he said.

Skin punch biopsies also may help investigators to understand how nerve regeneration occurs after an injury in diabetic patients, Dr. Polydefkis said. In a study of patients who applied capsaicin topically to their distal thighs—causing denervation of the epidermis—he and his colleagues found the rate of regeneration depended in part on the patient's baseline ENFD. Diabetic patients had a significantly lower regeneration rate than did healthy control patients even after adjustment for baseline differences; the rate was even lower among diabetic patients with neuropathy than in those without it. After 100 days, neither group of diabetic patients regenerated their ENFD to baseline levels (Brain 2004;127:1606–17). (See photos.)

These results suggest that an improvement in regeneration could be an early signal of effectiveness of an intervention for neuropathy, he said.

Epidermal denervation indicates small fiber neuropathy in a newly diagnosed diabetic with foot symptoms.

Skin punch biopsies from a healthy individual: normal baseline epidermal nerve fiber density (top, red arrows); complete denervation 2 days after topical capsaicin; and return of normal nerve fiber density after 29 days. Photos Courtesy Dr. Michael Polydefkis and Peter Hauer/Johns Hopkins Cutaneous Nerve Laboratory

WASHINGTON — Analysis of skin punch biopsy specimens may help predict diabetic neuropathy in at-risk patients, diagnose the condition earlier, and assess treatment response, Dr. Michael Polydefkis said at the annual scientific sessions of the American Diabetes Association.

Skin punch biopsy specimens contain small unmyelinated nerve fibers that are damaged in early diabetes. Normative data have shown that the degree of involvement is related to the degree of glucose dysmetabolism, said Dr. Polydefkis, codirector of the cutaneous nerve laboratory at Johns Hopkins University, Baltimore.

Analysis of skin biopsy specimens can help exclude other potential causes of painful feet such as radiculopathy, Morton's neuroma, tarsal tunnel syndrome, and intrinsic foot disease, he said.

A 3-mm diameter, circular skin punch biopsy specimen (about half the size of a pencil eraser) is sliced into about 60 sections, 4 of which are randomly selected for analysis to reduce sample bias since there may be differences in nerve density in different parts of the specimen. Biopsies should be taken at the ankle or other distal sites in patients with early neuropathic symptoms but at the thigh or other proximal sites in those with advanced neuropathy, he said.

In a study of 73 patients with an unknown cause of peripheral neuropathy, Dr. Polydefkis and his associates found that epidermal nerve fiber density (ENFD) in skin punch biopsy specimens was a good marker of early neuropathy. Of the 73 patients, 25 were diagnosed with impaired glucose tolerance (IGT) and 16 had diabetes.

The ENFD in biopsy specimens of patients with diabetes or IGT was significantly reduced, compared with healthy control patients. In specimens from the distal leg but not the distal or proximal thigh, diabetic patients had significantly lower ENFD than did patients with IGT. Yet nerve conduction studies yielded normal results on average in both groups.

Dr. Polydefkis and his associates concluded that the measurement of ENFD in skin punch biopsies is a more sensitive marker for detecting neuropathy early than are nerve conduction studies that test the function of large myelinated nerve fibers (Neurology 2003;60:108–11).

At the end of an average follow-up of 4.4 years, repeat testing in 29 patients showed that decline in ENFD was greatest in patients with diabetes, followed by patients with IGT and patients with idiopathic neuropathy. ENFD was essentially stable in 10 healthy control patients. “This longitudinal data provide some of the best evidence that the association between IGT and neuropathy is, in fact, causal,” Dr. Polydefkis said.

Information on nerve morphology also can be extracted from skin punch biopsy specimens. In one study, investigators performed nerve conduction studies, quantitative sensory testing, and skin punch biopsies in the proximal thigh and distal leg at baseline and after a mean of 19 months of follow-up in 15 patients with foot pain but few or no symptoms of neuropathy (6 with diabetes, 1 with AIDS, 1 with paclitaxel toxicity, 7 with an idiopathic nature) and 15 age-matched, healthy control patients.

At baseline, patients had significantly lower ENFD in the distal leg than did controls. At follow-up, the ENFD had declined in both biopsy locations but only by a significant amount in the distal leg, compared with the controls (Neurology 2003;61:631–6).

The results of that study provide “evidence that the skin biopsy can be used to predict development of neuropathy,” Dr. Polydefkis said.

Clinically meaningful changes in ENFD are on the order of a loss of 2–3 nerve fibers per millimeter. Diabetic patients who present with painful peripheral neuropathy appear to have ENFD losses in the range of 1 fiber/mm per year, while losses for those with established diabetes and peripheral neuropathy may be slightly higher, he said.

Skin punch biopsies also may help investigators to understand how nerve regeneration occurs after an injury in diabetic patients, Dr. Polydefkis said. In a study of patients who applied capsaicin topically to their distal thighs—causing denervation of the epidermis—he and his colleagues found the rate of regeneration depended in part on the patient's baseline ENFD. Diabetic patients had a significantly lower regeneration rate than did healthy control patients even after adjustment for baseline differences; the rate was even lower among diabetic patients with neuropathy than in those without it. After 100 days, neither group of diabetic patients regenerated their ENFD to baseline levels (Brain 2004;127:1606–17). (See photos.)

These results suggest that an improvement in regeneration could be an early signal of effectiveness of an intervention for neuropathy, he said.

Epidermal denervation indicates small fiber neuropathy in a newly diagnosed diabetic with foot symptoms.

Skin punch biopsies from a healthy individual: normal baseline epidermal nerve fiber density (top, red arrows); complete denervation 2 days after topical capsaicin; and return of normal nerve fiber density after 29 days. Photos Courtesy Dr. Michael Polydefkis and Peter Hauer/Johns Hopkins Cutaneous Nerve Laboratory

WASHINGTON — Analysis of skin punch biopsy specimens may help predict diabetic neuropathy in at-risk patients, diagnose the condition earlier, and assess treatment response, Dr. Michael Polydefkis said at the annual scientific sessions of the American Diabetes Association.

Skin punch biopsy specimens contain small unmyelinated nerve fibers that are damaged in early diabetes. Normative data have shown that the degree of involvement is related to the degree of glucose dysmetabolism, said Dr. Polydefkis, codirector of the cutaneous nerve laboratory at Johns Hopkins University, Baltimore.

Analysis of skin biopsy specimens can help exclude other potential causes of painful feet such as radiculopathy, Morton's neuroma, tarsal tunnel syndrome, and intrinsic foot disease, he said.

A 3-mm diameter, circular skin punch biopsy specimen (about half the size of a pencil eraser) is sliced into about 60 sections, 4 of which are randomly selected for analysis to reduce sample bias since there may be differences in nerve density in different parts of the specimen. Biopsies should be taken at the ankle or other distal sites in patients with early neuropathic symptoms but at the thigh or other proximal sites in those with advanced neuropathy, he said.

In a study of 73 patients with an unknown cause of peripheral neuropathy, Dr. Polydefkis and his associates found that epidermal nerve fiber density (ENFD) in skin punch biopsy specimens was a good marker of early neuropathy. Of the 73 patients, 25 were diagnosed with impaired glucose tolerance (IGT) and 16 had diabetes.

The ENFD in biopsy specimens of patients with diabetes or IGT was significantly reduced, compared with healthy control patients. In specimens from the distal leg but not the distal or proximal thigh, diabetic patients had significantly lower ENFD than did patients with IGT. Yet nerve conduction studies yielded normal results on average in both groups.

Dr. Polydefkis and his associates concluded that the measurement of ENFD in skin punch biopsies is a more sensitive marker for detecting neuropathy early than are nerve conduction studies that test the function of large myelinated nerve fibers (Neurology 2003;60:108–11).

At the end of an average follow-up of 4.4 years, repeat testing in 29 patients showed that decline in ENFD was greatest in patients with diabetes, followed by patients with IGT and patients with idiopathic neuropathy. ENFD was essentially stable in 10 healthy control patients. “This longitudinal data provide some of the best evidence that the association between IGT and neuropathy is, in fact, causal,” Dr. Polydefkis said.

Information on nerve morphology also can be extracted from skin punch biopsy specimens. In one study, investigators performed nerve conduction studies, quantitative sensory testing, and skin punch biopsies in the proximal thigh and distal leg at baseline and after a mean of 19 months of follow-up in 15 patients with foot pain but few or no symptoms of neuropathy (6 with diabetes, 1 with AIDS, 1 with paclitaxel toxicity, 7 with an idiopathic nature) and 15 age-matched, healthy control patients.

At baseline, patients had significantly lower ENFD in the distal leg than did controls. At follow-up, the ENFD had declined in both biopsy locations but only by a significant amount in the distal leg, compared with the controls (Neurology 2003;61:631–6).

The results of that study provide “evidence that the skin biopsy can be used to predict development of neuropathy,” Dr. Polydefkis said.

Clinically meaningful changes in ENFD are on the order of a loss of 2–3 nerve fibers per millimeter. Diabetic patients who present with painful peripheral neuropathy appear to have ENFD losses in the range of 1 fiber/mm per year, while losses for those with established diabetes and peripheral neuropathy may be slightly higher, he said.

Skin punch biopsies also may help investigators to understand how nerve regeneration occurs after an injury in diabetic patients, Dr. Polydefkis said. In a study of patients who applied capsaicin topically to their distal thighs—causing denervation of the epidermis—he and his colleagues found the rate of regeneration depended in part on the patient's baseline ENFD. Diabetic patients had a significantly lower regeneration rate than did healthy control patients even after adjustment for baseline differences; the rate was even lower among diabetic patients with neuropathy than in those without it. After 100 days, neither group of diabetic patients regenerated their ENFD to baseline levels (Brain 2004;127:1606–17). (See photos.)

These results suggest that an improvement in regeneration could be an early signal of effectiveness of an intervention for neuropathy, he said.

Epidermal denervation indicates small fiber neuropathy in a newly diagnosed diabetic with foot symptoms.

Skin punch biopsies from a healthy individual: normal baseline epidermal nerve fiber density (top, red arrows); complete denervation 2 days after topical capsaicin; and return of normal nerve fiber density after 29 days. Photos Courtesy Dr. Michael Polydefkis and Peter Hauer/Johns Hopkins Cutaneous Nerve Laboratory

WASHINGTON — Corneal confocal microscopy can noninvasively reveal neuropathy early in diabetes and help in monitoring treatment response, speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but lacks sensitivity. Nerve conduction studies are time-consuming and only measure the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on patient responses. Skin nerve biopsies can provide much information, but are “highly invasive,” said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), she and her colleagues obtain real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye. They studied 183 people including diabetics without neuropathy; diabetics with mild, moderate, or severe neuropathy; and controls without diabetes,

Diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

Measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, using the Neuropathy Disability Score.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to assess the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes (average age, 41 years).

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity and significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy (average age, 55).

At 6 months after transplantation, repeat scans in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly.

In a related study, microscopy had sensitivity (71%) and specificity (77%) comparable with skin punch biopsy specimens (59% and 90%, respectively).

Confocal micrographs show nerves in a control patient without neuropathy.

By comparison, nerve density is lower in a diabetic patient with neuropathy. Photos courtesy Mitra Tavakoli

WASHINGTON — Corneal confocal microscopy can noninvasively reveal neuropathy early in diabetes and help in monitoring treatment response, speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but lacks sensitivity. Nerve conduction studies are time-consuming and only measure the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on patient responses. Skin nerve biopsies can provide much information, but are “highly invasive,” said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), she and her colleagues obtain real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye. They studied 183 people including diabetics without neuropathy; diabetics with mild, moderate, or severe neuropathy; and controls without diabetes,

Diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

Measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, using the Neuropathy Disability Score.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to assess the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes (average age, 41 years).

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity and significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy (average age, 55).

At 6 months after transplantation, repeat scans in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly.

In a related study, microscopy had sensitivity (71%) and specificity (77%) comparable with skin punch biopsy specimens (59% and 90%, respectively).

Confocal micrographs show nerves in a control patient without neuropathy.

By comparison, nerve density is lower in a diabetic patient with neuropathy. Photos courtesy Mitra Tavakoli

WASHINGTON — Corneal confocal microscopy can noninvasively reveal neuropathy early in diabetes and help in monitoring treatment response, speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but lacks sensitivity. Nerve conduction studies are time-consuming and only measure the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on patient responses. Skin nerve biopsies can provide much information, but are “highly invasive,” said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), she and her colleagues obtain real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye. They studied 183 people including diabetics without neuropathy; diabetics with mild, moderate, or severe neuropathy; and controls without diabetes,

Diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

Measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, using the Neuropathy Disability Score.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to assess the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes (average age, 41 years).

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity and significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy (average age, 55).

At 6 months after transplantation, repeat scans in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly.

In a related study, microscopy had sensitivity (71%) and specificity (77%) comparable with skin punch biopsy specimens (59% and 90%, respectively).

Confocal micrographs show nerves in a control patient without neuropathy.

By comparison, nerve density is lower in a diabetic patient with neuropathy. Photos courtesy Mitra Tavakoli

PRAGUE — Neither elective cesarean section nor planned vaginal birth has yet been convincingly shown to provide the lower rate of perinatal and maternal complications in studies.

Most trials have not been randomized, have often reached opposing results, and have not compared elective C-section against planned vaginal birth, stymieing clinicians' ability to conclude which may offer the least amount of risk to the newborn and mother, Dr. Ola Didrik Saugstad said at the 20th European Congress of Perinatal Medicine.

Retrospective comparisons of elective repeat C-sections and trial of labor (prior to a repeat C-section) in term infants have alternately suggested that elective repeat C-section may increase an infant's risk of respiratory problems, hyperbilirubinemia, and a longer length of stay in the hospital (Pediatrics 1997;100:348–53), yet also confer a reduced risk of sepsis and an Apgar score of less than 6 at 1 minute.

Another study found no difference between the two delivery strategies in overall perinatal or maternal morbidity or mortality (N. Engl. J. Med. 1996;335:689–95), said Dr. Saugstad of the department of pediatric research at the Rikshospitalet University Hospital, Oslo.

Dr. Saugstad and his colleagues have conducted a prospective study comparing 17,828 planned vaginal deliveries and 825 elective C-sections that occurred during January through June 1999 in Norway. There was no difference between the two groups in neonatal mortality or the percentage of infants with an Apgar score of less than 7 at 1 minute or less than 4 at 5 minutes. But significantly more infants who were delivered with a planned C-section were transferred to the neonatal ICU (18%) than were babies born with a planned vaginal delivery (9%). Babies delivered by a planned C-section also had significantly higher rates of pulmonary disorders, hypoglycemia, and anemia. Vaginally born infants were delivered at an older mean gestational age than C-section infants (39.4 weeks vs. 38.4 weeks) in the study, which is in press for the American Journal of Obstetrics and Gynecology.

In studies involving small or extremely- low-birth-weight infants, comparisons of elective versus selective C-section, C-section with labor versus C-section without labor, and vaginal delivery versus C-section have generally shown no significant differences in perinatal or maternal outcomes. But these studies have mostly been retrospective and have often compared infants of dissimilar gestational age and birth weight, Dr. Saugstad said.

A Cochrane review of six studies involving 122 women found no significant differences between elective and selective C-section on perinatal and maternal outcomes, citing that there was not enough evidence to evaluate the policy of elective C-section for small babies (Cochrane Database Syst. Rev. 2001;2:CD000078).

In a retrospective cohort study, C-section with labor was associated with significantly higher rates of grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, and neurodevelopmental impairment at 18–22 months of age. But newborns who were delivered by C-section without labor had a significantly older gestational age than those who were delivered by C-section with labor. Correction for this and other risk factors made the difference in complications nonsignificant (Am. J. Obstet. Gynecol. 2003;189:501–6).

In a smaller retrospective study of extremely-low-birth-weight infants with a gestational age of less than 26 weeks at birth, significantly more neonates born vaginally survived than (21 of 27) than did those born by C-section (9 of 21).

Vaginally born infants tended to have lower rates of mechanical intervention, surfactant treatment, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, or sepsis. But infants who were delivered by C-section had significantly lower birth weight, umbilical artery pH, and rectal temperature than vaginally delivered babies (Am. J. Perinatol. 2003;20:181–8).

Results from the multicenter, randomized Term Breech Trial showed that vaginally born infants had significantly greater mortality (5%) at up to 6 weeks of follow-up than those delivered by C-section (1.6%) (Lancet 2000;356:1375–83). But there was no difference in either maternal (Am. J. Obstet. Gynecol. 2004;191:917–27) or neonatal outcomes (Am. J. Obstet. Gynecol. 2004;191:864–71) after 2 years of follow-up, Dr. Saugstad said.

PRAGUE — Neither elective cesarean section nor planned vaginal birth has yet been convincingly shown to provide the lower rate of perinatal and maternal complications in studies.

Most trials have not been randomized, have often reached opposing results, and have not compared elective C-section against planned vaginal birth, stymieing clinicians' ability to conclude which may offer the least amount of risk to the newborn and mother, Dr. Ola Didrik Saugstad said at the 20th European Congress of Perinatal Medicine.

Retrospective comparisons of elective repeat C-sections and trial of labor (prior to a repeat C-section) in term infants have alternately suggested that elective repeat C-section may increase an infant's risk of respiratory problems, hyperbilirubinemia, and a longer length of stay in the hospital (Pediatrics 1997;100:348–53), yet also confer a reduced risk of sepsis and an Apgar score of less than 6 at 1 minute.

Another study found no difference between the two delivery strategies in overall perinatal or maternal morbidity or mortality (N. Engl. J. Med. 1996;335:689–95), said Dr. Saugstad of the department of pediatric research at the Rikshospitalet University Hospital, Oslo.

Dr. Saugstad and his colleagues have conducted a prospective study comparing 17,828 planned vaginal deliveries and 825 elective C-sections that occurred during January through June 1999 in Norway. There was no difference between the two groups in neonatal mortality or the percentage of infants with an Apgar score of less than 7 at 1 minute or less than 4 at 5 minutes. But significantly more infants who were delivered with a planned C-section were transferred to the neonatal ICU (18%) than were babies born with a planned vaginal delivery (9%). Babies delivered by a planned C-section also had significantly higher rates of pulmonary disorders, hypoglycemia, and anemia. Vaginally born infants were delivered at an older mean gestational age than C-section infants (39.4 weeks vs. 38.4 weeks) in the study, which is in press for the American Journal of Obstetrics and Gynecology.

In studies involving small or extremely- low-birth-weight infants, comparisons of elective versus selective C-section, C-section with labor versus C-section without labor, and vaginal delivery versus C-section have generally shown no significant differences in perinatal or maternal outcomes. But these studies have mostly been retrospective and have often compared infants of dissimilar gestational age and birth weight, Dr. Saugstad said.

A Cochrane review of six studies involving 122 women found no significant differences between elective and selective C-section on perinatal and maternal outcomes, citing that there was not enough evidence to evaluate the policy of elective C-section for small babies (Cochrane Database Syst. Rev. 2001;2:CD000078).

In a retrospective cohort study, C-section with labor was associated with significantly higher rates of grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, and neurodevelopmental impairment at 18–22 months of age. But newborns who were delivered by C-section without labor had a significantly older gestational age than those who were delivered by C-section with labor. Correction for this and other risk factors made the difference in complications nonsignificant (Am. J. Obstet. Gynecol. 2003;189:501–6).

In a smaller retrospective study of extremely-low-birth-weight infants with a gestational age of less than 26 weeks at birth, significantly more neonates born vaginally survived than (21 of 27) than did those born by C-section (9 of 21).

Vaginally born infants tended to have lower rates of mechanical intervention, surfactant treatment, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, or sepsis. But infants who were delivered by C-section had significantly lower birth weight, umbilical artery pH, and rectal temperature than vaginally delivered babies (Am. J. Perinatol. 2003;20:181–8).

Results from the multicenter, randomized Term Breech Trial showed that vaginally born infants had significantly greater mortality (5%) at up to 6 weeks of follow-up than those delivered by C-section (1.6%) (Lancet 2000;356:1375–83). But there was no difference in either maternal (Am. J. Obstet. Gynecol. 2004;191:917–27) or neonatal outcomes (Am. J. Obstet. Gynecol. 2004;191:864–71) after 2 years of follow-up, Dr. Saugstad said.

PRAGUE — Neither elective cesarean section nor planned vaginal birth has yet been convincingly shown to provide the lower rate of perinatal and maternal complications in studies.

Most trials have not been randomized, have often reached opposing results, and have not compared elective C-section against planned vaginal birth, stymieing clinicians' ability to conclude which may offer the least amount of risk to the newborn and mother, Dr. Ola Didrik Saugstad said at the 20th European Congress of Perinatal Medicine.

Retrospective comparisons of elective repeat C-sections and trial of labor (prior to a repeat C-section) in term infants have alternately suggested that elective repeat C-section may increase an infant's risk of respiratory problems, hyperbilirubinemia, and a longer length of stay in the hospital (Pediatrics 1997;100:348–53), yet also confer a reduced risk of sepsis and an Apgar score of less than 6 at 1 minute.

Another study found no difference between the two delivery strategies in overall perinatal or maternal morbidity or mortality (N. Engl. J. Med. 1996;335:689–95), said Dr. Saugstad of the department of pediatric research at the Rikshospitalet University Hospital, Oslo.

Dr. Saugstad and his colleagues have conducted a prospective study comparing 17,828 planned vaginal deliveries and 825 elective C-sections that occurred during January through June 1999 in Norway. There was no difference between the two groups in neonatal mortality or the percentage of infants with an Apgar score of less than 7 at 1 minute or less than 4 at 5 minutes. But significantly more infants who were delivered with a planned C-section were transferred to the neonatal ICU (18%) than were babies born with a planned vaginal delivery (9%). Babies delivered by a planned C-section also had significantly higher rates of pulmonary disorders, hypoglycemia, and anemia. Vaginally born infants were delivered at an older mean gestational age than C-section infants (39.4 weeks vs. 38.4 weeks) in the study, which is in press for the American Journal of Obstetrics and Gynecology.

In studies involving small or extremely- low-birth-weight infants, comparisons of elective versus selective C-section, C-section with labor versus C-section without labor, and vaginal delivery versus C-section have generally shown no significant differences in perinatal or maternal outcomes. But these studies have mostly been retrospective and have often compared infants of dissimilar gestational age and birth weight, Dr. Saugstad said.

A Cochrane review of six studies involving 122 women found no significant differences between elective and selective C-section on perinatal and maternal outcomes, citing that there was not enough evidence to evaluate the policy of elective C-section for small babies (Cochrane Database Syst. Rev. 2001;2:CD000078).

In a retrospective cohort study, C-section with labor was associated with significantly higher rates of grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, and neurodevelopmental impairment at 18–22 months of age. But newborns who were delivered by C-section without labor had a significantly older gestational age than those who were delivered by C-section with labor. Correction for this and other risk factors made the difference in complications nonsignificant (Am. J. Obstet. Gynecol. 2003;189:501–6).

In a smaller retrospective study of extremely-low-birth-weight infants with a gestational age of less than 26 weeks at birth, significantly more neonates born vaginally survived than (21 of 27) than did those born by C-section (9 of 21).

Vaginally born infants tended to have lower rates of mechanical intervention, surfactant treatment, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, or sepsis. But infants who were delivered by C-section had significantly lower birth weight, umbilical artery pH, and rectal temperature than vaginally delivered babies (Am. J. Perinatol. 2003;20:181–8).

Results from the multicenter, randomized Term Breech Trial showed that vaginally born infants had significantly greater mortality (5%) at up to 6 weeks of follow-up than those delivered by C-section (1.6%) (Lancet 2000;356:1375–83). But there was no difference in either maternal (Am. J. Obstet. Gynecol. 2004;191:917–27) or neonatal outcomes (Am. J. Obstet. Gynecol. 2004;191:864–71) after 2 years of follow-up, Dr. Saugstad said.

PRAGUE — Normative values for mean blood glucose levels during the first trimester may be much lower than previously believed, Dr. Yariv Yogev reported at the 20th European Congress of Perinatal Medicine.

This lower-than-expected glycemic profile may suggest new targets for glycemic control during pregnancy complicated by diabetes, said Dr. Yogev of the department of obstetrics and gynecology at Rabin Medical Center, Petah Tikva, Israel.

The study included 62 healthy, nondiabetic women in their first trimester of pregnancy (average of 10 weeks' gestation). The investigators fit the women with continuous glucose monitoring devices that measured their blood glucose levels every 5 minutes for 72 hours.

The overall mean blood glucose (79.3 mg/dL) and mean fasting blood glucose levels (75 mg/dL) were “much, much lower than was previously reported by others.” Mean nighttime blood glucose levels (66 mg/dL) “almost represented hypoglycemia,” but such values may actually represent “normal physiology during the first trimester in nondiabetic patients,” he said.

The postprandial glycemic profile of the women was the same after each meal. Mean blood glucose values started at 79 mg/dL just before a meal and rose to 106 mg/dL 60 minutes after the meal; it reached a high of 112 mg/dL 74 minutes after the meal. The values reached 99 mg/dL at 2 hours and 82 mg/dL at 3 hours.

The fasting and overall mean blood glucose levels were similar in 18 obese (defined as a body mass index greater than 27.3 kg/m

The women as a whole were at least one standard deviation below the recommended threshold for the treatment of diabetes during pregnancy, he said.

PRAGUE — Normative values for mean blood glucose levels during the first trimester may be much lower than previously believed, Dr. Yariv Yogev reported at the 20th European Congress of Perinatal Medicine.

This lower-than-expected glycemic profile may suggest new targets for glycemic control during pregnancy complicated by diabetes, said Dr. Yogev of the department of obstetrics and gynecology at Rabin Medical Center, Petah Tikva, Israel.

The study included 62 healthy, nondiabetic women in their first trimester of pregnancy (average of 10 weeks' gestation). The investigators fit the women with continuous glucose monitoring devices that measured their blood glucose levels every 5 minutes for 72 hours.

The overall mean blood glucose (79.3 mg/dL) and mean fasting blood glucose levels (75 mg/dL) were “much, much lower than was previously reported by others.” Mean nighttime blood glucose levels (66 mg/dL) “almost represented hypoglycemia,” but such values may actually represent “normal physiology during the first trimester in nondiabetic patients,” he said.

The postprandial glycemic profile of the women was the same after each meal. Mean blood glucose values started at 79 mg/dL just before a meal and rose to 106 mg/dL 60 minutes after the meal; it reached a high of 112 mg/dL 74 minutes after the meal. The values reached 99 mg/dL at 2 hours and 82 mg/dL at 3 hours.

The fasting and overall mean blood glucose levels were similar in 18 obese (defined as a body mass index greater than 27.3 kg/m

The women as a whole were at least one standard deviation below the recommended threshold for the treatment of diabetes during pregnancy, he said.

PRAGUE — Normative values for mean blood glucose levels during the first trimester may be much lower than previously believed, Dr. Yariv Yogev reported at the 20th European Congress of Perinatal Medicine.

This lower-than-expected glycemic profile may suggest new targets for glycemic control during pregnancy complicated by diabetes, said Dr. Yogev of the department of obstetrics and gynecology at Rabin Medical Center, Petah Tikva, Israel.

The study included 62 healthy, nondiabetic women in their first trimester of pregnancy (average of 10 weeks' gestation). The investigators fit the women with continuous glucose monitoring devices that measured their blood glucose levels every 5 minutes for 72 hours.

The overall mean blood glucose (79.3 mg/dL) and mean fasting blood glucose levels (75 mg/dL) were “much, much lower than was previously reported by others.” Mean nighttime blood glucose levels (66 mg/dL) “almost represented hypoglycemia,” but such values may actually represent “normal physiology during the first trimester in nondiabetic patients,” he said.

The postprandial glycemic profile of the women was the same after each meal. Mean blood glucose values started at 79 mg/dL just before a meal and rose to 106 mg/dL 60 minutes after the meal; it reached a high of 112 mg/dL 74 minutes after the meal. The values reached 99 mg/dL at 2 hours and 82 mg/dL at 3 hours.

The fasting and overall mean blood glucose levels were similar in 18 obese (defined as a body mass index greater than 27.3 kg/m

The women as a whole were at least one standard deviation below the recommended threshold for the treatment of diabetes during pregnancy, he said.

PRAGUE — Very few women in their first pregnancy appear to request an elective cesarean section but when they do, few would do it again, according to a study of nearly 400 German and U.S. women presented at the 20th European Congress of Perinatal Medicine.

In a prospective study of maternal preferences for birth, questionnaires were completed by 55 of 64 U.S. and 342 of 366 German women. All of the women were primigravid with singleton pregnancies and in good health when they completed questionnaires in the third trimester and 8–12 weeks after their pregnancy, Dr. Beate Schücking reported.

In 2005, the 29% rate of cesarean section in Germany closely mirrored that of the United States, said Dr. Schücking of the University of Osnabrück (Germany).

In the third trimester, nearly all U.S. (95%) and German (96%) women said that they preferred vaginal delivery. The women reported that they believed a vaginal birth would offer more security, an easier recovery, and less pain and injury than would a cesarean section.

Three U.S. women were indecisive about which method they preferred. The 13 German women who preferred a C-section said they wanted the surgical procedure because of anxiety, and they wanted to avoid pain and injuries, to have security for their baby, and to deliver a breech-positioned fetus safely.

Unlike the women who decided that they wanted a vaginal delivery early in their pregnancy, the women who preferred a C-section were indecisive about which method they preferred until the end of their pregnancy. Those who preferred a C-section were younger, had lower scores of well-being, and were more likely to be unmarried.

These results were “quite consistent” with a Swedish study of 3,061 pregnant women that found that 8% would opt for a C-section. That 8% had more anxiety and depression than those who desired a vaginal delivery (BJOG 2002;109:618–23). Although the women in that study were not all first-time mothers, they, too, were more likely to be single, younger, and have already had a negative birth experience.

In reality, spontaneous vaginal births occurred at lower rates among the U.S. (64%) and German (61%) women than they would have liked. The actual C-section rates were higher among the U.S. (20%) and German (26%) women than their stated preference. Vaginal operative births occurred in 16% of U.S. and 13% of German women.

In the German sample, 89% of the women who had a spontaneous vaginal delivery indicated that they would like to repeat that method if they had a second child. But only 18% of those who received an elective C-section said that they would like to repeat it with a second baby. Few women who had an unplanned C-section (14%) or vaginal operative delivery (9%) wanted to repeat those methods.

The fact that very few women in the two groups requested C-section may indicate that “rising [C-section] rates are not really due to maternal request” but are most likely to occur among “vulnerable, anxious women,” she said.

“For me, the question is if surgery is really the best way to answer a mental problem.”

PRAGUE — Very few women in their first pregnancy appear to request an elective cesarean section but when they do, few would do it again, according to a study of nearly 400 German and U.S. women presented at the 20th European Congress of Perinatal Medicine.

In a prospective study of maternal preferences for birth, questionnaires were completed by 55 of 64 U.S. and 342 of 366 German women. All of the women were primigravid with singleton pregnancies and in good health when they completed questionnaires in the third trimester and 8–12 weeks after their pregnancy, Dr. Beate Schücking reported.

In 2005, the 29% rate of cesarean section in Germany closely mirrored that of the United States, said Dr. Schücking of the University of Osnabrück (Germany).

In the third trimester, nearly all U.S. (95%) and German (96%) women said that they preferred vaginal delivery. The women reported that they believed a vaginal birth would offer more security, an easier recovery, and less pain and injury than would a cesarean section.

Three U.S. women were indecisive about which method they preferred. The 13 German women who preferred a C-section said they wanted the surgical procedure because of anxiety, and they wanted to avoid pain and injuries, to have security for their baby, and to deliver a breech-positioned fetus safely.

Unlike the women who decided that they wanted a vaginal delivery early in their pregnancy, the women who preferred a C-section were indecisive about which method they preferred until the end of their pregnancy. Those who preferred a C-section were younger, had lower scores of well-being, and were more likely to be unmarried.

These results were “quite consistent” with a Swedish study of 3,061 pregnant women that found that 8% would opt for a C-section. That 8% had more anxiety and depression than those who desired a vaginal delivery (BJOG 2002;109:618–23). Although the women in that study were not all first-time mothers, they, too, were more likely to be single, younger, and have already had a negative birth experience.

In reality, spontaneous vaginal births occurred at lower rates among the U.S. (64%) and German (61%) women than they would have liked. The actual C-section rates were higher among the U.S. (20%) and German (26%) women than their stated preference. Vaginal operative births occurred in 16% of U.S. and 13% of German women.

In the German sample, 89% of the women who had a spontaneous vaginal delivery indicated that they would like to repeat that method if they had a second child. But only 18% of those who received an elective C-section said that they would like to repeat it with a second baby. Few women who had an unplanned C-section (14%) or vaginal operative delivery (9%) wanted to repeat those methods.

The fact that very few women in the two groups requested C-section may indicate that “rising [C-section] rates are not really due to maternal request” but are most likely to occur among “vulnerable, anxious women,” she said.

“For me, the question is if surgery is really the best way to answer a mental problem.”

PRAGUE — Very few women in their first pregnancy appear to request an elective cesarean section but when they do, few would do it again, according to a study of nearly 400 German and U.S. women presented at the 20th European Congress of Perinatal Medicine.

In a prospective study of maternal preferences for birth, questionnaires were completed by 55 of 64 U.S. and 342 of 366 German women. All of the women were primigravid with singleton pregnancies and in good health when they completed questionnaires in the third trimester and 8–12 weeks after their pregnancy, Dr. Beate Schücking reported.

In 2005, the 29% rate of cesarean section in Germany closely mirrored that of the United States, said Dr. Schücking of the University of Osnabrück (Germany).

In the third trimester, nearly all U.S. (95%) and German (96%) women said that they preferred vaginal delivery. The women reported that they believed a vaginal birth would offer more security, an easier recovery, and less pain and injury than would a cesarean section.

Three U.S. women were indecisive about which method they preferred. The 13 German women who preferred a C-section said they wanted the surgical procedure because of anxiety, and they wanted to avoid pain and injuries, to have security for their baby, and to deliver a breech-positioned fetus safely.

Unlike the women who decided that they wanted a vaginal delivery early in their pregnancy, the women who preferred a C-section were indecisive about which method they preferred until the end of their pregnancy. Those who preferred a C-section were younger, had lower scores of well-being, and were more likely to be unmarried.

These results were “quite consistent” with a Swedish study of 3,061 pregnant women that found that 8% would opt for a C-section. That 8% had more anxiety and depression than those who desired a vaginal delivery (BJOG 2002;109:618–23). Although the women in that study were not all first-time mothers, they, too, were more likely to be single, younger, and have already had a negative birth experience.

In reality, spontaneous vaginal births occurred at lower rates among the U.S. (64%) and German (61%) women than they would have liked. The actual C-section rates were higher among the U.S. (20%) and German (26%) women than their stated preference. Vaginal operative births occurred in 16% of U.S. and 13% of German women.

In the German sample, 89% of the women who had a spontaneous vaginal delivery indicated that they would like to repeat that method if they had a second child. But only 18% of those who received an elective C-section said that they would like to repeat it with a second baby. Few women who had an unplanned C-section (14%) or vaginal operative delivery (9%) wanted to repeat those methods.

The fact that very few women in the two groups requested C-section may indicate that “rising [C-section] rates are not really due to maternal request” but are most likely to occur among “vulnerable, anxious women,” she said.

“For me, the question is if surgery is really the best way to answer a mental problem.”

WASHINGTON — Corneal confocal microscopy provides a means for noninvasively diagnosing neuropathy early on in diabetic patients and for following the course of the disease during treatment, several speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but it lacks sensitivity, said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Nerve conduction studies are time-consuming and are reliable only in measuring the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on the patient's response to take measurements. Skin nerve biopsies can provide much information, but are “highly invasive,” she said.

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), Ms. Tavakoli and her colleagues are able to obtain in vivo, real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye.

She and her coinvestigators studied 183 people including control patients without diabetes, diabetic patients without neuropathy, and diabetic patients with mild, moderate, or severe neuropathy.

They found that diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

The measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, as measured by the Neuropathy Disability Score.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to show the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes who had an average age of 41 years.

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity as well as significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy who had an average age of 55 years.

At 6 months after transplantation, repeat scans in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly. Other posttransplantation studies that have employed electrophysiology and quantitative sensory testing have been able to detect improvements in large fiber function after 3–4 years, unlike the early detection of small fiber repair at 6 months in this study, Ms. Tavakoli reported.

In the laboratory of Nathan Efron, Ph.D.—one of Ms. Tavakoli's collaborators—the microscopy technique has proved to have sensitivity (71%) and specificity (77%) comparable with the histopathologic examination of skin punch biopsy specimens (59% and 90%, respectively) when both are compared with the “gold standard” Neuropathic Disability Score.

Dr. Efron has used confocal microscopy to monitor longitudinal changes in corneal morphology in patients who have received myopic laser in situ keratomileusis (LASIK), which involves cutting a flap of the cornea, irradiating the corneal stroma with a laser, and replacing the flap. The LASIK procedure severs corneal nerves in the subbasal nerve plexus where most of the corneal nerves reside. Several weeks after the surgery, confocal microscopy shows a “hazy image” devoid of any nerve fibers. At 3 months, a few nerve fragments can be seen, and at 6 months a few continuous nerves begin to appear (Optom. Vis. Sci. 2003;80:690–7).

“Certainly, this has implications with respect to diabetic patients who are having this LASIK procedure,” said Dr. Efron, research professor at Queensland University of Technology, Brisbane, Australia.

Confocal micrographs show nerves in a control patient without neuropathy.

By comparison, nerve density is lower in a diabetic patient with neuropathy. Photos courtesy Mitra Tavakoli

WASHINGTON — Corneal confocal microscopy provides a means for noninvasively diagnosing neuropathy early on in diabetic patients and for following the course of the disease during treatment, several speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but it lacks sensitivity, said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Nerve conduction studies are time-consuming and are reliable only in measuring the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on the patient's response to take measurements. Skin nerve biopsies can provide much information, but are “highly invasive,” she said.

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), Ms. Tavakoli and her colleagues are able to obtain in vivo, real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye.

She and her coinvestigators studied 183 people including control patients without diabetes, diabetic patients without neuropathy, and diabetic patients with mild, moderate, or severe neuropathy.

They found that diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

The measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, as measured by the Neuropathy Disability Score.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to show the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes who had an average age of 41 years.

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity as well as significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy who had an average age of 55 years.

At 6 months after transplantation, repeat scans in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly. Other posttransplantation studies that have employed electrophysiology and quantitative sensory testing have been able to detect improvements in large fiber function after 3–4 years, unlike the early detection of small fiber repair at 6 months in this study, Ms. Tavakoli reported.

In the laboratory of Nathan Efron, Ph.D.—one of Ms. Tavakoli's collaborators—the microscopy technique has proved to have sensitivity (71%) and specificity (77%) comparable with the histopathologic examination of skin punch biopsy specimens (59% and 90%, respectively) when both are compared with the “gold standard” Neuropathic Disability Score.

Dr. Efron has used confocal microscopy to monitor longitudinal changes in corneal morphology in patients who have received myopic laser in situ keratomileusis (LASIK), which involves cutting a flap of the cornea, irradiating the corneal stroma with a laser, and replacing the flap. The LASIK procedure severs corneal nerves in the subbasal nerve plexus where most of the corneal nerves reside. Several weeks after the surgery, confocal microscopy shows a “hazy image” devoid of any nerve fibers. At 3 months, a few nerve fragments can be seen, and at 6 months a few continuous nerves begin to appear (Optom. Vis. Sci. 2003;80:690–7).

“Certainly, this has implications with respect to diabetic patients who are having this LASIK procedure,” said Dr. Efron, research professor at Queensland University of Technology, Brisbane, Australia.

Confocal micrographs show nerves in a control patient without neuropathy.

By comparison, nerve density is lower in a diabetic patient with neuropathy. Photos courtesy Mitra Tavakoli

WASHINGTON — Corneal confocal microscopy provides a means for noninvasively diagnosing neuropathy early on in diabetic patients and for following the course of the disease during treatment, several speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but it lacks sensitivity, said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Nerve conduction studies are time-consuming and are reliable only in measuring the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on the patient's response to take measurements. Skin nerve biopsies can provide much information, but are “highly invasive,” she said.

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), Ms. Tavakoli and her colleagues are able to obtain in vivo, real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye.

She and her coinvestigators studied 183 people including control patients without diabetes, diabetic patients without neuropathy, and diabetic patients with mild, moderate, or severe neuropathy.

They found that diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

The measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, as measured by the Neuropathy Disability Score.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to show the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes who had an average age of 41 years.

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity as well as significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy who had an average age of 55 years.

At 6 months after transplantation, repeat scans in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly. Other posttransplantation studies that have employed electrophysiology and quantitative sensory testing have been able to detect improvements in large fiber function after 3–4 years, unlike the early detection of small fiber repair at 6 months in this study, Ms. Tavakoli reported.

In the laboratory of Nathan Efron, Ph.D.—one of Ms. Tavakoli's collaborators—the microscopy technique has proved to have sensitivity (71%) and specificity (77%) comparable with the histopathologic examination of skin punch biopsy specimens (59% and 90%, respectively) when both are compared with the “gold standard” Neuropathic Disability Score.

Dr. Efron has used confocal microscopy to monitor longitudinal changes in corneal morphology in patients who have received myopic laser in situ keratomileusis (LASIK), which involves cutting a flap of the cornea, irradiating the corneal stroma with a laser, and replacing the flap. The LASIK procedure severs corneal nerves in the subbasal nerve plexus where most of the corneal nerves reside. Several weeks after the surgery, confocal microscopy shows a “hazy image” devoid of any nerve fibers. At 3 months, a few nerve fragments can be seen, and at 6 months a few continuous nerves begin to appear (Optom. Vis. Sci. 2003;80:690–7).

“Certainly, this has implications with respect to diabetic patients who are having this LASIK procedure,” said Dr. Efron, research professor at Queensland University of Technology, Brisbane, Australia.

Confocal micrographs show nerves in a control patient without neuropathy.

By comparison, nerve density is lower in a diabetic patient with neuropathy. Photos courtesy Mitra Tavakoli

PRAGUE — New insights into the pathophysiologic changes of preeclampsia that occur in the placenta are helping researchers to develop potential early screening tests for the disease using biomarkers in maternal blood, Dr. Wolfgang Holzgreve said at the 20th European Congress of Perinatal Medicine.

The current line of research into the cause of preeclampsia originates from observations that associated the long-term presence of fetal cells and DNA in maternal blood with autoimmune diseases such as scleroderma and conditions such as polymorphic eruptions of pregnancy (Lancet 1998;352:1898–901). About 8 years ago, Dr. Holzgreve and his colleagues at the University of Basel (Switzerland) began to recognize that the association between microchimerism and maternal disease might extend to preeclampsia and play a role in its pathophysiology.

In Dr. Holzgreve's lab, researchers found many more fetal cells and DNA in the blood of women with preeclampsia than in women with normal pregnancies. Reports from his lab indicated that the elevated levels of free fetal DNA in maternal blood positively correlated with the presence and severity of preeclampsia in mothers in a dose-response-like effect (Am. J. Obstet. Gynecol. 2001;184:414–9).

Similar observations were made regarding the effect of the total amount of free maternal DNA in a pregnant woman's plasma. The total free maternal DNA seemed to be a marker for the amount of damage that preeclampsia causes to the endothelial cells that line the liver and kidneys, as well as the circulatory system, he said.

The first insult to occur in preeclampsia is an invasion of trophoblasts that causes impairment of the spiral arteries and placental changes. The investigators hypothesized that the excess fetal cells and DNA going into the maternal circulation cause leukocyte activation and an “inflammatory-like reaction” in the peripheral endothelial system (Placenta 2005;26:515–26).

Anatomists working with Dr. Holzgreve's group have calculated that about 3 billion mitoses occur in the placenta each day—no cancer in humans has such a high rate of division—and this activity produces about 3.6 g of new syncytium each day from all of the placental cell divisions. But only 0.6 g of new syncytium is incorporated into the placenta each day. Thus, about 3 g of syncytial tissue travels into the intervillous space and into the maternal circulation each day.

Normally the multinucleated cells and membrane-bound particles of syncytium undergo controlled apoptosis. But if the placenta is hypoxic from trophoblast invasion, a separate pathway of aponecrotic shedding occurs, releasing materials that are toxic to the maternal epithelial system. In vitro tests in Dr. Holzgreve's lab have shown that cultures of endothelial cells from umbilical veins break down after exposure to particles of placental syncytium.

Recent evidence has shown that the body traps the materials shed from the placenta by an extracellular filamentous network produced by neutrophils, which is the same as the defensive mechanism described for neutrophils that trap pathogenic bacteria (Science 2004;303:1532–5). These networks are present in higher abundance in preeclamptic women than in pregnant control women, Dr. Holzgreve said.

The model of excess fetal cells and free DNA also fits with the knowledge that the highest risk for preeclampsia occurs in first pregnancies (in which the mother has not been exposed to her partner's genes), in women who have a new pregnancy from a different man, and in cases of ovum donation in which all of the fetal material is foreign.

Because clinical signs and symptoms are so poor at predicting who will have preeclampsia, Dr. Holzgreve and his colleagues have tried, using the increase in free fetal DNA in the maternal circulation, to predict preeclampsia as early in pregnancy as possible. Recent studies have indicated that women with preeclampsia have significantly increased levels of free fetal DNA in their blood beginning at a gestational age of 20 weeks, which could have potential as an early test for the disease, he said.

“What needs to be done now is a big, multicenter study to see what the predictive tests are,” he said. “Then the vision would be that there is first-trimester screening of nuchal translucency and second-trimester screening including free fetal DNA” in maternal blood.

PRAGUE — New insights into the pathophysiologic changes of preeclampsia that occur in the placenta are helping researchers to develop potential early screening tests for the disease using biomarkers in maternal blood, Dr. Wolfgang Holzgreve said at the 20th European Congress of Perinatal Medicine.

The current line of research into the cause of preeclampsia originates from observations that associated the long-term presence of fetal cells and DNA in maternal blood with autoimmune diseases such as scleroderma and conditions such as polymorphic eruptions of pregnancy (Lancet 1998;352:1898–901). About 8 years ago, Dr. Holzgreve and his colleagues at the University of Basel (Switzerland) began to recognize that the association between microchimerism and maternal disease might extend to preeclampsia and play a role in its pathophysiology.

In Dr. Holzgreve's lab, researchers found many more fetal cells and DNA in the blood of women with preeclampsia than in women with normal pregnancies. Reports from his lab indicated that the elevated levels of free fetal DNA in maternal blood positively correlated with the presence and severity of preeclampsia in mothers in a dose-response-like effect (Am. J. Obstet. Gynecol. 2001;184:414–9).

Similar observations were made regarding the effect of the total amount of free maternal DNA in a pregnant woman's plasma. The total free maternal DNA seemed to be a marker for the amount of damage that preeclampsia causes to the endothelial cells that line the liver and kidneys, as well as the circulatory system, he said.

The first insult to occur in preeclampsia is an invasion of trophoblasts that causes impairment of the spiral arteries and placental changes. The investigators hypothesized that the excess fetal cells and DNA going into the maternal circulation cause leukocyte activation and an “inflammatory-like reaction” in the peripheral endothelial system (Placenta 2005;26:515–26).

Anatomists working with Dr. Holzgreve's group have calculated that about 3 billion mitoses occur in the placenta each day—no cancer in humans has such a high rate of division—and this activity produces about 3.6 g of new syncytium each day from all of the placental cell divisions. But only 0.6 g of new syncytium is incorporated into the placenta each day. Thus, about 3 g of syncytial tissue travels into the intervillous space and into the maternal circulation each day.

Normally the multinucleated cells and membrane-bound particles of syncytium undergo controlled apoptosis. But if the placenta is hypoxic from trophoblast invasion, a separate pathway of aponecrotic shedding occurs, releasing materials that are toxic to the maternal epithelial system. In vitro tests in Dr. Holzgreve's lab have shown that cultures of endothelial cells from umbilical veins break down after exposure to particles of placental syncytium.

Recent evidence has shown that the body traps the materials shed from the placenta by an extracellular filamentous network produced by neutrophils, which is the same as the defensive mechanism described for neutrophils that trap pathogenic bacteria (Science 2004;303:1532–5). These networks are present in higher abundance in preeclamptic women than in pregnant control women, Dr. Holzgreve said.

The model of excess fetal cells and free DNA also fits with the knowledge that the highest risk for preeclampsia occurs in first pregnancies (in which the mother has not been exposed to her partner's genes), in women who have a new pregnancy from a different man, and in cases of ovum donation in which all of the fetal material is foreign.

Because clinical signs and symptoms are so poor at predicting who will have preeclampsia, Dr. Holzgreve and his colleagues have tried, using the increase in free fetal DNA in the maternal circulation, to predict preeclampsia as early in pregnancy as possible. Recent studies have indicated that women with preeclampsia have significantly increased levels of free fetal DNA in their blood beginning at a gestational age of 20 weeks, which could have potential as an early test for the disease, he said.

“What needs to be done now is a big, multicenter study to see what the predictive tests are,” he said. “Then the vision would be that there is first-trimester screening of nuchal translucency and second-trimester screening including free fetal DNA” in maternal blood.

PRAGUE — New insights into the pathophysiologic changes of preeclampsia that occur in the placenta are helping researchers to develop potential early screening tests for the disease using biomarkers in maternal blood, Dr. Wolfgang Holzgreve said at the 20th European Congress of Perinatal Medicine.

The current line of research into the cause of preeclampsia originates from observations that associated the long-term presence of fetal cells and DNA in maternal blood with autoimmune diseases such as scleroderma and conditions such as polymorphic eruptions of pregnancy (Lancet 1998;352:1898–901). About 8 years ago, Dr. Holzgreve and his colleagues at the University of Basel (Switzerland) began to recognize that the association between microchimerism and maternal disease might extend to preeclampsia and play a role in its pathophysiology.

In Dr. Holzgreve's lab, researchers found many more fetal cells and DNA in the blood of women with preeclampsia than in women with normal pregnancies. Reports from his lab indicated that the elevated levels of free fetal DNA in maternal blood positively correlated with the presence and severity of preeclampsia in mothers in a dose-response-like effect (Am. J. Obstet. Gynecol. 2001;184:414–9).

Similar observations were made regarding the effect of the total amount of free maternal DNA in a pregnant woman's plasma. The total free maternal DNA seemed to be a marker for the amount of damage that preeclampsia causes to the endothelial cells that line the liver and kidneys, as well as the circulatory system, he said.

The first insult to occur in preeclampsia is an invasion of trophoblasts that causes impairment of the spiral arteries and placental changes. The investigators hypothesized that the excess fetal cells and DNA going into the maternal circulation cause leukocyte activation and an “inflammatory-like reaction” in the peripheral endothelial system (Placenta 2005;26:515–26).

Anatomists working with Dr. Holzgreve's group have calculated that about 3 billion mitoses occur in the placenta each day—no cancer in humans has such a high rate of division—and this activity produces about 3.6 g of new syncytium each day from all of the placental cell divisions. But only 0.6 g of new syncytium is incorporated into the placenta each day. Thus, about 3 g of syncytial tissue travels into the intervillous space and into the maternal circulation each day.

Normally the multinucleated cells and membrane-bound particles of syncytium undergo controlled apoptosis. But if the placenta is hypoxic from trophoblast invasion, a separate pathway of aponecrotic shedding occurs, releasing materials that are toxic to the maternal epithelial system. In vitro tests in Dr. Holzgreve's lab have shown that cultures of endothelial cells from umbilical veins break down after exposure to particles of placental syncytium.

Recent evidence has shown that the body traps the materials shed from the placenta by an extracellular filamentous network produced by neutrophils, which is the same as the defensive mechanism described for neutrophils that trap pathogenic bacteria (Science 2004;303:1532–5). These networks are present in higher abundance in preeclamptic women than in pregnant control women, Dr. Holzgreve said.

The model of excess fetal cells and free DNA also fits with the knowledge that the highest risk for preeclampsia occurs in first pregnancies (in which the mother has not been exposed to her partner's genes), in women who have a new pregnancy from a different man, and in cases of ovum donation in which all of the fetal material is foreign.

Because clinical signs and symptoms are so poor at predicting who will have preeclampsia, Dr. Holzgreve and his colleagues have tried, using the increase in free fetal DNA in the maternal circulation, to predict preeclampsia as early in pregnancy as possible. Recent studies have indicated that women with preeclampsia have significantly increased levels of free fetal DNA in their blood beginning at a gestational age of 20 weeks, which could have potential as an early test for the disease, he said.

“What needs to be done now is a big, multicenter study to see what the predictive tests are,” he said. “Then the vision would be that there is first-trimester screening of nuchal translucency and second-trimester screening including free fetal DNA” in maternal blood.

PRAGUE — Very few women in their first pregnancy appear to request an elective cesarean section but when they do, few would do it again, according to a study of nearly 400 German and U.S. women presented at the 20th European Congress of Perinatal Medicine.

In a prospective study of maternal preferences for birth, questionnaires were completed by 55 of 64 American and 342 of 366 German women.

All of the women were primigravid with singleton pregnancies and in good health when they completed questionnaires in the third trimester and 8–12 weeks after their pregnancy, Dr. Beate Schücking reported.

In 2005, the 29% rate of cesarean section in Germany closely mirrored that of the United States, said Dr. Schücking of the University of Osnabrück (Germany).

In the third trimester, nearly all U.S. (95%) and German (96%) women said that they preferred vaginal delivery. The women reported that they believed a vaginal birth would offer more security, an easier recovery, and less pain and injury than would a cesarean section.

Three of the 55 women in the United States were indecisive about which method they preferred. The 13 German women who preferred a C-section said they wanted the surgical procedure because of anxiety, and they wanted to avoid pain and injuries, to have security for their baby, and to deliver a breech-positioned fetus safely.

Unlike the women who decided that they wanted a vaginal delivery early in their pregnancy, the women who preferred a C-section were indecisive about which method they preferred until the end of their pregnancy.

Those who preferred a C-section were younger, had lower scores of well-being, and were more likely to be unmarried.

These results were “quite consistent” with a Swedish study of 3,061 pregnant women that found that 8% would opt for a C-section and that that same 8% had more anxiety and depression than those who desired a vaginal delivery (BJOG 2002;109:618–23).

Although the women in that study were not all first-time mothers, they, too, were more likely to be single, younger, and have already had a negative birth experience. “The women got quite a different birth experience from what they had wished to have,” Dr. Schücking noted.

In reality, spontaneous vaginal births occurred at lower rates among the U.S. (64%) and German (61%) women than they would have liked. The actual C-section rates were higher among the U.S. (20%) and German (26%) women than their stated preference. Vaginal operative births occurred in 16% of U.S. and 13% of German women

Spontaneous vaginal birth was more satisfying to the women than elective C-section, followed by vaginal operative birth and C-section after the onset of labor.

In the German sample, 89% of the women who had a spontaneous vaginal delivery indicated that they would like to repeat that method if they had a second child.

But only 18% of those who received an elective C-section said that they would like to repeat it with a second baby. Few women who had an unplanned C-section (14%) or vaginal operative delivery (9%) wanted to repeat those methods.

The well-being of both U.S. and German women was significantly lower in the postpartum than antenatal period, although this did not correlate with the method of birth, Dr. Schücking said.

The fact that very few women in the two groups requested a cesarean section may indicate that “rising [C-section] rates are not really due to maternal request” but are most likely to occur among “vulnerable, anxious women,” she said.

“For me, the question is if surgery is really the best way to answer a mental problem.”

PRAGUE — Very few women in their first pregnancy appear to request an elective cesarean section but when they do, few would do it again, according to a study of nearly 400 German and U.S. women presented at the 20th European Congress of Perinatal Medicine.

In a prospective study of maternal preferences for birth, questionnaires were completed by 55 of 64 American and 342 of 366 German women.

All of the women were primigravid with singleton pregnancies and in good health when they completed questionnaires in the third trimester and 8–12 weeks after their pregnancy, Dr. Beate Schücking reported.

In 2005, the 29% rate of cesarean section in Germany closely mirrored that of the United States, said Dr. Schücking of the University of Osnabrück (Germany).

In the third trimester, nearly all U.S. (95%) and German (96%) women said that they preferred vaginal delivery. The women reported that they believed a vaginal birth would offer more security, an easier recovery, and less pain and injury than would a cesarean section.

Three of the 55 women in the United States were indecisive about which method they preferred. The 13 German women who preferred a C-section said they wanted the surgical procedure because of anxiety, and they wanted to avoid pain and injuries, to have security for their baby, and to deliver a breech-positioned fetus safely.

Unlike the women who decided that they wanted a vaginal delivery early in their pregnancy, the women who preferred a C-section were indecisive about which method they preferred until the end of their pregnancy.

Those who preferred a C-section were younger, had lower scores of well-being, and were more likely to be unmarried.

These results were “quite consistent” with a Swedish study of 3,061 pregnant women that found that 8% would opt for a C-section and that that same 8% had more anxiety and depression than those who desired a vaginal delivery (BJOG 2002;109:618–23).

Although the women in that study were not all first-time mothers, they, too, were more likely to be single, younger, and have already had a negative birth experience. “The women got quite a different birth experience from what they had wished to have,” Dr. Schücking noted.

In reality, spontaneous vaginal births occurred at lower rates among the U.S. (64%) and German (61%) women than they would have liked. The actual C-section rates were higher among the U.S. (20%) and German (26%) women than their stated preference. Vaginal operative births occurred in 16% of U.S. and 13% of German women

Spontaneous vaginal birth was more satisfying to the women than elective C-section, followed by vaginal operative birth and C-section after the onset of labor.

In the German sample, 89% of the women who had a spontaneous vaginal delivery indicated that they would like to repeat that method if they had a second child.

But only 18% of those who received an elective C-section said that they would like to repeat it with a second baby. Few women who had an unplanned C-section (14%) or vaginal operative delivery (9%) wanted to repeat those methods.

The well-being of both U.S. and German women was significantly lower in the postpartum than antenatal period, although this did not correlate with the method of birth, Dr. Schücking said.

The fact that very few women in the two groups requested a cesarean section may indicate that “rising [C-section] rates are not really due to maternal request” but are most likely to occur among “vulnerable, anxious women,” she said.

“For me, the question is if surgery is really the best way to answer a mental problem.”

PRAGUE — Very few women in their first pregnancy appear to request an elective cesarean section but when they do, few would do it again, according to a study of nearly 400 German and U.S. women presented at the 20th European Congress of Perinatal Medicine.

In a prospective study of maternal preferences for birth, questionnaires were completed by 55 of 64 American and 342 of 366 German women.

All of the women were primigravid with singleton pregnancies and in good health when they completed questionnaires in the third trimester and 8–12 weeks after their pregnancy, Dr. Beate Schücking reported.

In 2005, the 29% rate of cesarean section in Germany closely mirrored that of the United States, said Dr. Schücking of the University of Osnabrück (Germany).

In the third trimester, nearly all U.S. (95%) and German (96%) women said that they preferred vaginal delivery. The women reported that they believed a vaginal birth would offer more security, an easier recovery, and less pain and injury than would a cesarean section.

Three of the 55 women in the United States were indecisive about which method they preferred. The 13 German women who preferred a C-section said they wanted the surgical procedure because of anxiety, and they wanted to avoid pain and injuries, to have security for their baby, and to deliver a breech-positioned fetus safely.

Unlike the women who decided that they wanted a vaginal delivery early in their pregnancy, the women who preferred a C-section were indecisive about which method they preferred until the end of their pregnancy.

Those who preferred a C-section were younger, had lower scores of well-being, and were more likely to be unmarried.

These results were “quite consistent” with a Swedish study of 3,061 pregnant women that found that 8% would opt for a C-section and that that same 8% had more anxiety and depression than those who desired a vaginal delivery (BJOG 2002;109:618–23).

Although the women in that study were not all first-time mothers, they, too, were more likely to be single, younger, and have already had a negative birth experience. “The women got quite a different birth experience from what they had wished to have,” Dr. Schücking noted.

In reality, spontaneous vaginal births occurred at lower rates among the U.S. (64%) and German (61%) women than they would have liked. The actual C-section rates were higher among the U.S. (20%) and German (26%) women than their stated preference. Vaginal operative births occurred in 16% of U.S. and 13% of German women

Spontaneous vaginal birth was more satisfying to the women than elective C-section, followed by vaginal operative birth and C-section after the onset of labor.

In the German sample, 89% of the women who had a spontaneous vaginal delivery indicated that they would like to repeat that method if they had a second child.

But only 18% of those who received an elective C-section said that they would like to repeat it with a second baby. Few women who had an unplanned C-section (14%) or vaginal operative delivery (9%) wanted to repeat those methods.

The well-being of both U.S. and German women was significantly lower in the postpartum than antenatal period, although this did not correlate with the method of birth, Dr. Schücking said.

The fact that very few women in the two groups requested a cesarean section may indicate that “rising [C-section] rates are not really due to maternal request” but are most likely to occur among “vulnerable, anxious women,” she said.

“For me, the question is if surgery is really the best way to answer a mental problem.”

PRAGUE — Preeclampsia may significantly worsen some perinatal outcomes in growth-restricted infants, according to a review of infants born to mothers with and without preeclampsia.

In a study of growth-restricted neonates born at a gestational age older than 24 weeks, 25 infants whose mothers had preeclampsia had significantly worse psychomotor development on the Ages and Stages Questionnaire than did 46 infants born to mothers who did not have preeclampsia, Dr. Elisenda Eixarch reported in a poster session at the 20th European Congress of Perinatal Medicine.

In those neurologic evaluations, which were prospectively evaluated at 24 months, the children born to preeclamptic mothers scored at a significantly lower centile on the fine motor and problem-solving dimensions than did children of nonpreeclamptic mothers. The other three dimensions of the questionnaire (communication, gross motor, and personal-social) were worse in children of mothers with preeclampsia than in those of mothers without preeclampsia but not significantly so, according to Dr. Eixarch of the department of obstetrics and gynecology at the Hospital Clinic, Barcelona.

All of the infants in the study were estimated to have a birth weight below the 10th percentile.

Dr. Eixarch and her colleagues adjusted the analysis of each dimension of the questionnaire for birth weight and gestational age, because those two variables were significantly higher among infants born to mothers without preeclampsia than among those born to mothers with preeclampsia.

Compared with infants born to nonpreeclamptic mothers, the babies who had preeclamptic mothers had significantly higher rates of cesarean section (36% vs. 70%) and “significant neonatal neurological morbidity” (3% vs. 13%)—that is, seizures, grade 2 or 3 intraventricular hemorrhage, or hypoxic encephalopathy—and a significantly longer length of stay in the neonatal ICU (5.4 days vs. 18.3 days).

PRAGUE — Preeclampsia may significantly worsen some perinatal outcomes in growth-restricted infants, according to a review of infants born to mothers with and without preeclampsia.

In a study of growth-restricted neonates born at a gestational age older than 24 weeks, 25 infants whose mothers had preeclampsia had significantly worse psychomotor development on the Ages and Stages Questionnaire than did 46 infants born to mothers who did not have preeclampsia, Dr. Elisenda Eixarch reported in a poster session at the 20th European Congress of Perinatal Medicine.

In those neurologic evaluations, which were prospectively evaluated at 24 months, the children born to preeclamptic mothers scored at a significantly lower centile on the fine motor and problem-solving dimensions than did children of nonpreeclamptic mothers. The other three dimensions of the questionnaire (communication, gross motor, and personal-social) were worse in children of mothers with preeclampsia than in those of mothers without preeclampsia but not significantly so, according to Dr. Eixarch of the department of obstetrics and gynecology at the Hospital Clinic, Barcelona.

All of the infants in the study were estimated to have a birth weight below the 10th percentile.

Dr. Eixarch and her colleagues adjusted the analysis of each dimension of the questionnaire for birth weight and gestational age, because those two variables were significantly higher among infants born to mothers without preeclampsia than among those born to mothers with preeclampsia.

Compared with infants born to nonpreeclamptic mothers, the babies who had preeclamptic mothers had significantly higher rates of cesarean section (36% vs. 70%) and “significant neonatal neurological morbidity” (3% vs. 13%)—that is, seizures, grade 2 or 3 intraventricular hemorrhage, or hypoxic encephalopathy—and a significantly longer length of stay in the neonatal ICU (5.4 days vs. 18.3 days).

PRAGUE — Preeclampsia may significantly worsen some perinatal outcomes in growth-restricted infants, according to a review of infants born to mothers with and without preeclampsia.

In a study of growth-restricted neonates born at a gestational age older than 24 weeks, 25 infants whose mothers had preeclampsia had significantly worse psychomotor development on the Ages and Stages Questionnaire than did 46 infants born to mothers who did not have preeclampsia, Dr. Elisenda Eixarch reported in a poster session at the 20th European Congress of Perinatal Medicine.

In those neurologic evaluations, which were prospectively evaluated at 24 months, the children born to preeclamptic mothers scored at a significantly lower centile on the fine motor and problem-solving dimensions than did children of nonpreeclamptic mothers. The other three dimensions of the questionnaire (communication, gross motor, and personal-social) were worse in children of mothers with preeclampsia than in those of mothers without preeclampsia but not significantly so, according to Dr. Eixarch of the department of obstetrics and gynecology at the Hospital Clinic, Barcelona.

All of the infants in the study were estimated to have a birth weight below the 10th percentile.

Dr. Eixarch and her colleagues adjusted the analysis of each dimension of the questionnaire for birth weight and gestational age, because those two variables were significantly higher among infants born to mothers without preeclampsia than among those born to mothers with preeclampsia.

Compared with infants born to nonpreeclamptic mothers, the babies who had preeclamptic mothers had significantly higher rates of cesarean section (36% vs. 70%) and “significant neonatal neurological morbidity” (3% vs. 13%)—that is, seizures, grade 2 or 3 intraventricular hemorrhage, or hypoxic encephalopathy—and a significantly longer length of stay in the neonatal ICU (5.4 days vs. 18.3 days).