p57Kip2, a potent inhibitor of several cyclin/cyclin dependent kinase complexes (CDK ), is a paternally imprinted gene in both humans and mice, and here we show that pregnant mice which are heterozygous for p57Kip2 deficiency display symptoms similar to preeclampsia. p57-/+ (heterozygotes for p57Kip2 ) female mice that were mated with p57-/+ males showed hypertension, proteinuria, thrombocytopenia, decreased anti-thrombin III activity, and increased endothelin levels during late pregnancy. In their kidneys, endotheliosis of glomeruli were recognized along with fibrinoid or hyalinoid deposits. These characteristics were also observed in pregnant p57-/+ females that were mated with wild type males, but not in pregnant wild type females mated with p57-/+ males or wild type males. The pregnant p57-/+ mice had conceptuses both with and without p57Kip2 expression. The conceptuses without p57Kip2 expression showed trophoblastic hyperplasia, which mimics the hallmark proliferation of intermediate trophoblasts in clinical preeclampsia. It is suggested that the preeclampsia-like symptoms of the pregnant p57-/+ mice might have been induced by the conceptus(es) without p57Kip2 expression. In addition, pregnant p57-/+ mice might serve as a new animal model for preeclampsia characterized by trophoblastic hyperplasia.

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The uteroplacental circulation in the placenta can have a major impact on the fetus. Near infrared spectroscopy (NIRS) is the noninvasive method of measuring changes in blood volumes and oxygen concentrations in living tissue. The purpose of this study is to monitor changes in placental tissue oxygen index (TOI) levels, in patients with intrauterine fetal growth restriction during pregnancy, using NIRS. We measured placental TOI values of 15 normal pregnant woman and 15 patients with intrauterine growth restriction admitted to our hospital. The placenta was assessed by ultrasound examination and NIRS was performed on all patients. The TOI values of the IUGR group when hospitalized was 78.6 +/- 1.6 (SD). This value was significantly higher than that of the controls (78.6 +/- 1.6 [SD] versus 70.2 +/- 0.4 [SD]). And the TOI values of the IUGR group, when measured before delivery, were 77.8 +/- 1.6 (SD). The TOI values of the IUGR group before delivery were significantly higher than those of the control group (77.8 +/- 1.6 [SD] versus 70.3 +/- 0.4 [SD]). We propose that NIRS is a candidate, noninvasive method for assessing placental oxygen dynamics on a real-time basis. In the near future it may contribute to perinatal medical practice.

We investigated coagulation/fibrinolysis parameters for significant differences between patients with early-onset severe preeclampsia (< 32 weeks gestation, wG) and those with late-onset severe preeclampsia (Ն 32 wG). A decrease in antithrombin (AT), protein C (PC), and free protein S (PS) activities and an increase in plasmin-␣2-plasmin inhibitor complex (PIC), thrombin-antithrombin complex (TAT), and FDP D-dimer (D-dimer) were observed. However, there were no statistical differences between the two groups. Once preeclampsia occurred and it developed severe, the changes in coagulation/fibrinolysis parameters became more severe in spite of early-onset preeclampsia or late-onset preeclampsia. We also investigated coagulation/fibrinolysis abnormalities in 101 patients with severe preeclampsia. A significant increase in WBC, RBC, Hb, Ht, TAT, PIC, and D-dimer and a significant decrease in platelet (Plt) counts and AT activity were observed. ⌬Plt (the difference between platelet counts in early gestation and before delivery) was Ϫ5.0 ‫ן‬ 10 4 /L in cases with severe preeclampsia. Among patients with severe preeclampsia, coagulation/fibrinolysis changes before delivery were typical for patients with cesarean section compared with those with successful vaginal delivery. These facts suggest that an excessive hypercoagulable state is associated with the termination of pregnancy resulting from the aggravation of preeclampsia. From the viewpoint of coagulation/fibrinolysis changes, the termination of pregnancy could be recommended when the levels of parameters exceed the following values; ⌬Plt >| Ϫ6.0 | ‫ן‬ 10 4 /L, D-dimer > 4 g/mL, AT activity < 79%, TAT > 26 ng/mL, and PIC > 1.2 g/mL. Particularly, ⌬Plt and D-dimer are useful bedside predictive markers in order to decide the optimal time for the termination of pregnancy in patients with severe preeclampsia.Objectives: Upon completion of the article, the reader should be able to 1) list some coagulation/fibrinolysis parameters that are abnormal in preeclamptic patients; and 2) state those values that should initiate prompt delivery of those patients. Accreditation: Tufts University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. TUSM takes full responsibility for the content, quality, and scientific integrity of this continuing education activity.

Multiple pregnancy and cervical shortening at 20-24 weeks of gestation was a stronger risk factor for preterm birth. Any pregnant woman being part-time employee or low educational level, having a male fetus and requiring steroid treatment should be watched for the development of preterm birth.