Skin capillary density drop reliably predicts preeclampsia

SAN FRANCISCO – A reduction in skin capillary density during pregnancy constitutes a novel independent and reliable noninvasive predictor of preeclampsia, according to Dr. Tarek Antonios of the University of London.

"Capillary density rarefaction is the most sensitive and specific predictor of preeclampsia to date. Combining capillary density rarefaction and the uterine artery Doppler pulsatility index increases the sensitivity of prediction to 86% and the specificity to 80%, figures that are by far more significant than any other published evidence about the clinical prediction of preeclampsia," he declared at the annual meeting of the American College of Cardiology.

Measurement of skin capillary density changes in pregnancy is inexpensive once the essential equipment – an intravital video microscope suitable for capillaroscopy – has been acquired, he added.

Cardiovascular risk factors known to predispose to preeclampsia include essential hypertension, diabetes, and obesity. Dr. Antonios and coworkers have surmised that the mechanism by which these disorders boost the risk of preeclampsia involves microcirculatory abnormalities and impaired tissue perfusion.

The investigators have developed a reproducible method of measuring skin capillary density on the dorsum of the hand. Further, they have demonstrated that reduced capillary density – which they term "structural capillary rarefaction" – beginning at about 20 weeks of gestation is a harbinger of subsequent onset of preeclampsia.

Dr. Antonios reported on 322 consecutive white women with singleton pregnancies, of whom 13 had a history of preeclampsia, 11 had a history of untreated stage 1 essential hypertension, and the rest were normotensive. They underwent five structured capillaroscopy assessments at 11-16 weeks’ of gestation, 20-24 weeks, 27-32 weeks, 34-38 weeks, and finally at 5-15 weeks post partum. The capillary density measurements were done in a temperature-controlled laboratory with a standardized technique.

Among the 305 women who completed the study, 16 (5%) developed preeclampsia. Four of the 16 (25%) had a history of preeclampsia, compared with just 3% of the 289 (1%) subjects with a normal pregnancy.

The women who became preeclamptic were also set apart by their mean 6.1 capillary/mm² reduction in density between the weeks 20-24 measurement and the weeks 11-16 baseline. In contrast, the women with normal pregnancies averaged a 1.0 capillary/mm² decrease during that time frame. Capillary rarefaction further increased over time in women who later developed preeclampsia: their mean reduction in density at the weeks 27-32 measurement was 11.4/mm², compared with the weeks 11-16 baseline, while the controls averaged a 2.1 capillary/mm² decrease.

In a multivariate regression analysis, the single strongest predictor of preeclampsia was a history of previous preeclampsia or essential hypertension, which was associated with a 35-fold increase in risk. Each 1 capillary/mm² reduction in density at 20-24 weeks was associated with a 3% increase in risk, while at 27-32 weeks every 1 capillary/mm² reduction in density conferred a 26% increase in the risk of preeclampsia.

Significant structural capillary rarefaction at weeks 27-32 had a 77% sensitivity and 77% specificity for subsequent preeclampsia. Combining an increased uterine artery Doppler pulsatility index with a finding of significant capillary density reduction at weeks 27-32 boosted the sensitivity to 86% and the specificity to 80%.

Given that only 16 participants in this study developed preeclampsia, the next step in this research is to conduct a large clinical trial to validate capillaroscopy as a clinical risk prediction tool with an eye toward its eventual integration into routine clinical practice, according to Dr. Antonios.

This study was funded by the British Heart Foundation. Dr. Antonios reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN FRANCISCO – A reduction in skin capillary density during pregnancy constitutes a novel independent and reliable noninvasive predictor of preeclampsia, according to Dr. Tarek Antonios of the University of London.

"Capillary density rarefaction is the most sensitive and specific predictor of preeclampsia to date. Combining capillary density rarefaction and the uterine artery Doppler pulsatility index increases the sensitivity of prediction to 86% and the specificity to 80%, figures that are by far more significant than any other published evidence about the clinical prediction of preeclampsia," he declared at the annual meeting of the American College of Cardiology.

Measurement of skin capillary density changes in pregnancy is inexpensive once the essential equipment – an intravital video microscope suitable for capillaroscopy – has been acquired, he added.

Cardiovascular risk factors known to predispose to preeclampsia include essential hypertension, diabetes, and obesity. Dr. Antonios and coworkers have surmised that the mechanism by which these disorders boost the risk of preeclampsia involves microcirculatory abnormalities and impaired tissue perfusion.

The investigators have developed a reproducible method of measuring skin capillary density on the dorsum of the hand. Further, they have demonstrated that reduced capillary density – which they term "structural capillary rarefaction" – beginning at about 20 weeks of gestation is a harbinger of subsequent onset of preeclampsia.

Dr. Antonios reported on 322 consecutive white women with singleton pregnancies, of whom 13 had a history of preeclampsia, 11 had a history of untreated stage 1 essential hypertension, and the rest were normotensive. They underwent five structured capillaroscopy assessments at 11-16 weeks’ of gestation, 20-24 weeks, 27-32 weeks, 34-38 weeks, and finally at 5-15 weeks post partum. The capillary density measurements were done in a temperature-controlled laboratory with a standardized technique.

Among the 305 women who completed the study, 16 (5%) developed preeclampsia. Four of the 16 (25%) had a history of preeclampsia, compared with just 3% of the 289 (1%) subjects with a normal pregnancy.

The women who became preeclamptic were also set apart by their mean 6.1 capillary/mm² reduction in density between the weeks 20-24 measurement and the weeks 11-16 baseline. In contrast, the women with normal pregnancies averaged a 1.0 capillary/mm² decrease during that time frame. Capillary rarefaction further increased over time in women who later developed preeclampsia: their mean reduction in density at the weeks 27-32 measurement was 11.4/mm², compared with the weeks 11-16 baseline, while the controls averaged a 2.1 capillary/mm² decrease.

In a multivariate regression analysis, the single strongest predictor of preeclampsia was a history of previous preeclampsia or essential hypertension, which was associated with a 35-fold increase in risk. Each 1 capillary/mm² reduction in density at 20-24 weeks was associated with a 3% increase in risk, while at 27-32 weeks every 1 capillary/mm² reduction in density conferred a 26% increase in the risk of preeclampsia.

Significant structural capillary rarefaction at weeks 27-32 had a 77% sensitivity and 77% specificity for subsequent preeclampsia. Combining an increased uterine artery Doppler pulsatility index with a finding of significant capillary density reduction at weeks 27-32 boosted the sensitivity to 86% and the specificity to 80%.

Given that only 16 participants in this study developed preeclampsia, the next step in this research is to conduct a large clinical trial to validate capillaroscopy as a clinical risk prediction tool with an eye toward its eventual integration into routine clinical practice, according to Dr. Antonios.

This study was funded by the British Heart Foundation. Dr. Antonios reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN FRANCISCO – A reduction in skin capillary density during pregnancy constitutes a novel independent and reliable noninvasive predictor of preeclampsia, according to Dr. Tarek Antonios of the University of London.

"Capillary density rarefaction is the most sensitive and specific predictor of preeclampsia to date. Combining capillary density rarefaction and the uterine artery Doppler pulsatility index increases the sensitivity of prediction to 86% and the specificity to 80%, figures that are by far more significant than any other published evidence about the clinical prediction of preeclampsia," he declared at the annual meeting of the American College of Cardiology.

Measurement of skin capillary density changes in pregnancy is inexpensive once the essential equipment – an intravital video microscope suitable for capillaroscopy – has been acquired, he added.

Cardiovascular risk factors known to predispose to preeclampsia include essential hypertension, diabetes, and obesity. Dr. Antonios and coworkers have surmised that the mechanism by which these disorders boost the risk of preeclampsia involves microcirculatory abnormalities and impaired tissue perfusion.

The investigators have developed a reproducible method of measuring skin capillary density on the dorsum of the hand. Further, they have demonstrated that reduced capillary density – which they term "structural capillary rarefaction" – beginning at about 20 weeks of gestation is a harbinger of subsequent onset of preeclampsia.

Dr. Antonios reported on 322 consecutive white women with singleton pregnancies, of whom 13 had a history of preeclampsia, 11 had a history of untreated stage 1 essential hypertension, and the rest were normotensive. They underwent five structured capillaroscopy assessments at 11-16 weeks’ of gestation, 20-24 weeks, 27-32 weeks, 34-38 weeks, and finally at 5-15 weeks post partum. The capillary density measurements were done in a temperature-controlled laboratory with a standardized technique.

Among the 305 women who completed the study, 16 (5%) developed preeclampsia. Four of the 16 (25%) had a history of preeclampsia, compared with just 3% of the 289 (1%) subjects with a normal pregnancy.

The women who became preeclamptic were also set apart by their mean 6.1 capillary/mm² reduction in density between the weeks 20-24 measurement and the weeks 11-16 baseline. In contrast, the women with normal pregnancies averaged a 1.0 capillary/mm² decrease during that time frame. Capillary rarefaction further increased over time in women who later developed preeclampsia: their mean reduction in density at the weeks 27-32 measurement was 11.4/mm², compared with the weeks 11-16 baseline, while the controls averaged a 2.1 capillary/mm² decrease.

In a multivariate regression analysis, the single strongest predictor of preeclampsia was a history of previous preeclampsia or essential hypertension, which was associated with a 35-fold increase in risk. Each 1 capillary/mm² reduction in density at 20-24 weeks was associated with a 3% increase in risk, while at 27-32 weeks every 1 capillary/mm² reduction in density conferred a 26% increase in the risk of preeclampsia.

Significant structural capillary rarefaction at weeks 27-32 had a 77% sensitivity and 77% specificity for subsequent preeclampsia. Combining an increased uterine artery Doppler pulsatility index with a finding of significant capillary density reduction at weeks 27-32 boosted the sensitivity to 86% and the specificity to 80%.

Given that only 16 participants in this study developed preeclampsia, the next step in this research is to conduct a large clinical trial to validate capillaroscopy as a clinical risk prediction tool with an eye toward its eventual integration into routine clinical practice, according to Dr. Antonios.

This study was funded by the British Heart Foundation. Dr. Antonios reported having no financial conflicts.

bjancin@frontlinemedcom.com