5) 妊娠高血圧症候群ならびに関連疾患の発症予知 : リスク因子の解明をめざして(シンポジウム2:周産期「妊娠高血圧症候群の基礎と臨床-予防・治療の新戦略に向けて」,第65回日本産科婦人科学会・学術講演会)

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As women with isolated proteinuria (new-onset proteinuria in the absence of hypertension) are more likely to progress to preeclampsia than women with gestational hypertension (new-onset hypertension in the absence of proteinuria), correct diagnosis of significant proteinuria is important. However, there are problems in methods for the detection of significant proteinuria in pregnancy; dipstick test and determination of protein concentration alone in the spot-urine sample (P test) are likely to over and underestimate risks of significant proteinuria, respectively; and the 24-h urine collection (24h urine test) is often incomplete. Repeated positive dipstick test results in two successive antenatal visits warrant a need for a confirmation test of significant proteinuria with determination of protein-to-creatinine ratio in the spot-urine (P/Cr test) to overcome disadvantages involved in dipstick test, P test and 24h urine test. Some women exhibit a gradual decline in antithrombin (AT) activity in pregnancy and to less than 65% peripartum (Pregnancy-induced AT deficiency, PIATD). The PIATD is an early stage leading to acute fatty liver of pregnancy. In addition, women with PIATD have approximately 50-fold higher risk of eclampsia compared those without PIATD. It is of note that prevalence of eclampsia was one per 28 teenagers with new onset hypertension, indicating that teenage pregnancy with hypertension is a strong risk factor for eclampsia. The PIATD is more likely to occur as the number of fetuses increases (approx. 1.0, 10%, and 40% for singleton, twin, and triplet pregnancies, respectively) and in women with hypertension, isolated proteinuria and/or edema. AT activity significantly correlates negatively with D-dimer, serum creatinine, and urate. AT molecule can escape from the circulating blood into the interstitial space in the presence of vascular endothelial dysfunction. These results suggested that women with PIATD suffer from a decreased plasma volume and enhanced coagulation-fibrinolysis as do women with preeclampsia. However, normotensive women account for 60% of women with PIATD. Correct diagnosis of significant proteinuria and the introduction of AT activity in obstetrical practice may show new aspects of diseases associated with preeclampsia and enhance "safety" in obstetrics. Our initiatives to predict onset of pregnancy-induced hypertension and associated diseasesTo explicate the risk factors of them. I. Problems in methods for the detection of significant proteinuria in pregnancy and for the diagnosis of gestational proteinuria. Dipstick test and P-test were likely to over and underestimate risks of significant proteinuria, respectively. Thus, the spot-urine protein-to-creatinine ratio (P/Cr test) would be used. The 24-h urine collection was often incomplete. Repeated positive dipstick test results in two successive antenatal visits warrant a need for a confirmation test of significant proteinuria. Women with new-onset proteinuria in the absence of hypertension may be more likely to progress to preeclampsia than women with a presumptive diagnosis of gestational hypertension, and the likelihood of progression may be significantly greater among women with earlier presentation. II. Relationship among eclampsia, pregnancy-induced hypertension (PIH) and pregnancyinduced antithrombin deficiency (PIATD). Hypertension alone was not a reliable predictor of eclampsia. More intensified monitoring of nulliparous women and teenaged girls with hypertension is needed in order to prevent eclampsia. A decrease in AT activity may occur in the absence of hypertension. Even in the absence of hypertension, a decreased plasma volume and enhanced coagulation-fibrinolysis seem to characterize women with PIATD. The monitoring of AT activity may help in distinguishing pregnant women with these insidious risks. II. Relationship between PIATD and gestational proteinuria. A considerable number of healthy women exhibit a reduced AT activity immediately before delivery. PIATD is more likely to occur as the number of fetuses increases (approx. 1.0%, 10%, and 40% for singleton, twin, and triplet pregnancies, respectively) and in women with hypertension, isolated proteinuria and/or edema. However, normotensive women account for 60% of women with PIATD. Antithrombin can escape from the blood into the interstitial space. Women with PIATD suffer from a decreased plasma volume and are more likely to develop liver dysfunction, irrespective of the presence or absence of hypertension. Because antithrombin activity continues to decrease until the time of delivery in women with PIATD, women with unrecognized PIATD may be identified as patients with so-called "acute fatty liver of pregnancy" if delivery is delayed. Enhanced thrombin generation was involved in the decrease in AT activity. AT activity can decrease in the absence of thrombocytopenia. The liver dysfunction that was seen in cases with severely depressed AT activity may have resulted from impairments in liver perfusion caused by microthromboses generated as a result of the relative lack of AT and/or the shortage of circulating plasma in women with reduced AT activities.
2013-11-01

5) 妊娠高血圧症候群ならびに関連疾患の発症予知 : リスク因子の解明をめざして(シンポジウム2:周産期「妊娠高血圧症候群の基礎と臨床-予防・治療の新戦略に向けて」,第65回日本産科婦人科学会・学術講演会)

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