Hisanori Minakami

Association of a decrease in antithrombin III activity with a perinatal elevation in aspartate aminotransferase in women with twin pregnancies: relevance to the HELLP syndrome

BACKGROUND/AIMS Decreased antithrombin III (AT-III) activity and/or thrombocytopenia associated with an elevated serum level of aspartate aminotransferase in late pregnancy can threaten the lives of both the mother and the fetus. We investigated whether antenatal declines in AT-III activity and the platelet count occur in late twin pregnancy and whether reduced AT-III activity and/or thrombocytopenia precedes an increase in the serum level of aspartate aminotransferase. METHODS The platelet count, AT-III activity, and the serum level of aspartate aminotransferase were determined weekly or biweekly in 237 women with twin pregnancies in a longitudinal and partly prospective study. RESULTS Both AT-III activity and the platelet count decreased gradually in the last month of pregnancy, irrespective of the presence or absence of clinical signs of pre-eclampsia. A perinatal elevation in aspartate aminotransferase occurred in 36 (15%) of 237 women. The risk of a perinatal elevation in aspartate amino-transferase increased as the antenatal AT-III activity and/or the platelet count decreased. Pre-eclampsia developed in 60 women (25%). The relative risk of a perinatal aspartate aminotransferase elevation (95% confidence interval) for the 60 women with pre-eclampsia, the 60 women with a platelet count < or = the 25th percentile (164 x 10(9)/1), and the 60 women with AT-III activity < or = the 25th percentile (76% of normal) was 1.9 (1.0 to 3.4), 4.1 (2.3 to 7.5), and 5.9 (3.2 to 11.1), respectively, compared with the remaining 177 women. CONCLUSIONS AT-III activity and platelet count gradually decreased in the last month of twin pregnancies. A perinatal aspartate aminotransferase elevation was preceded by marked decreases in these parameters in women with twin pregnancies. The monitoring of AT-III activity and platelet count in women who exhibit a gradual decline in these parameters may help to avoid the development of severe HELLP syndrome.

Meconium-stained amniotic fluid exhibits chemotactic activity for polymorphonuclear leukocytes in vitro

We have studied whether meconium-stained, turbid amniotic fluid (turbid AF) obtained during term pregnancy possesses chemotactic activity for polymorphonuclear leukocytes (PMNs) in the absence of clinically apparent infection. Eight samples of turbid AF were obtained from eight women who underwent a cesarean section (four emergency and four elective cesarean sections) in the absence of signs of clinical infection or fetal distress. Samples of clear AF obtained from nine women during an elective cesarean section served as a control. We used also a negative control (medium only) and a positive control containing 10 nM N-formyl-methionyl-leucyl-phenylalanine. The control or turbid AF specimen was placed in the lower compartment of a blind well chamber, and the PMN suspension was placed in the upper compartment. Following incubation, the number of PMNs that had migrated and passed through the filter to the AF was counted. The number of control PMNs that migrated to the turbid AF (200+/-59) was comparable to that of the positive (162+/-24) but significantly exceeded that of the clear AF (17+/-11; P < 0.0001) and of the negative control (25+/-9; P < 0.0001). Checkerboard assay indicated that the turbid AF exhibited a dose-dependent chemotactic activity for PMNs. The turbid AF contained higher levels of TNFalpha, IL-1beta and IL-8 than the clear AF. The concentration of IL-8 in the AF was correlated positively with the chemotactic activity of the AF (r = 0.733, P = 0.0005). Anti-human IL-8 antibody added in the turbid AF dose-dependently abolished the chemotactic activity of the turbid AF. It is concluded that meconium-stained AF is a chemoattractant for PMNs and that cytokines such as an IL-8 may be involved in this phenomenon.

Emergency Cervical Cerclage: Relation between Its Success, Preoperative Serum Level of C-Reactive Protein and WBC Count, and Degree of Cervical Dilatation

Objective: To assess the relation between the preoperative serum level of C-reactive protein (CRP) and the WBC count and the efficacy of emergency cervical cerclage. Study Design: We retrospectively reviewed the medical records of 17 women (16 singleton pregnancies and 1 twin pregnancy) who underwent emergency cervical cerclage (McDonald technique) between 21 and 26 weeks of gestation. The uterine cervix was dilated ≥3.0 cm and the intact (not ruptured) fetal membranes were visible or protruded into the vagina in all patients. The serum level of CRP and the WBC count were determined preoperatively and postoperatively. Emergency cervical cerclage was considered successful if delivery occurred ≥14 days after the procedure. Results: Emergency cervical cerclage was successful in 12 women, including the woman with a twin pregnancy, but failed in 5 women. The preoperative serum level of CRP and the WBC count were significantly lower and dilatation of the cervix was significantly less in the success group than in the failure group. Cerclage was successful in all eight patients with cervical dilatation ≤4.0 cm, but in only 4 of 9 patients with cervical dilatation >4.0 cm (p < 0.05). Cerclage was successful in all 11 women with a preoperative serum level of CRP ≤4.0 mg/dl and a WBC count ≤14,000/µl compared with 1 of 6 women with either a CRP level >4.0 mg/dl or a WBC count >14,000/µl (p < 0.01). Conclusion: A preoperative CRP value ≤4.0 mg/dl, a WBC count ≤14,000/µl, and cervical dilatation ≤4.0 cm were significantly associated with prolongation of pregnancy after emergency cervical cerclage.

Comparative Changes in Uterine Artery Blood Flow Waveforms in Singleton and Twin Pregnancies

We prospectively studied 99 women with uncomplicated singleton pregnancies and 24 women with uncomplicated twin pregnancies to examine the effect of the location of the placenta on the pulsatility index (PI) in the uterine arteries in twin pregnancies and to compare singleton and twin pregnancies with regard to changes in the PI of uterine arteries over the course of the pregnancy. The flow velocity waveforms in both the right and left parametrial uterine arteries were recorded longitudinally at 2-week intervals from a gestational age of 19 weeks until delivery. The location of the placenta was determined by real-time ultrasonography at 18–20 weeks of gestation to determine which uterine artery was the ipsilateral artery. In both the ipsilateral and contralateral uterine arteries, the PI exhibited a steady decrease toward term in singleton pregnancies. In twin pregnancies, the PI exhibited a steady decrease until 27 weeks of gestation and remained unchanged thereafter. The PI in the ipsilateral artery was consistently lower than that in the contralateral artery in singleton as well as twin pregnancies. The mean values of PI of the ipsilateral and contralateral uterine arteries of twin pregnancies was consistently lower than that of singleton pregnancies at any gestational week. These results suggest that the ipsilateral uterine artery contributes more to placental perfusion than does the contralateral uterine artery in twin as well as in singleton pregnancies. Twin pregnancies differed from singleton pregnancies with respect to changes in PI in the uterine artery according to gestational age. The PI of uterine arteries declined more rapidly and reached a plateau earlier in twin than in singleton pregnancies.

Treatment of Neonatal Infection Caused by Coxsackievirus B3

Four male infants with early neonatal infection caused by coxsackievirus B3 (presumed in one case) exhibited severe thrombocytopenia and liver dysfunction at presentation. The three infants who were administered human normal immunoglobulin within 3 days of disease onset survived, while the fourth infant, who received the preparation 6 days after disease onset, died.

First-trimester ultrasonographic investigation of cardiovascular anatomy in thoracoabdominally conjoined twins.

Abstract Options for the treatment of thoracoabdominally conjoined twins are dependent on the anatomy of the cardiovascular system. It is important to increase the accuracy of diagnosis of conjoined twins with a fused heart. Color Doppler imaging performed in a 23-year-old nulliparous Japanese woman at 12 weeks of gestation revealed synchronized blood flow in 2 aortic arches arising from a single heart. The patient underwent a therapeutic abortion, and the diagnosis of conjoined twins with a fused heart was confirmed. Thus, color Doppler imaging is useful for investigating the cardiovascular anatomy in conjoined twins suspected of having a fused heart, even in an early gestational age.

Risk of premature birth in multifetal pregnancy.

The risk of preterm delivery (< 37 weeks of gestation) is approximately nine times higher in women with multifetal pregnancies than in women with singleton pregnancies. However, it is possible that the risk will vary according to gestational week. To assess the risk of premature birth within 1 week by gestational age among multifetal pregnancies and compare the estimated risk with that of singleton pregnancies, we analyzed 6,036,475 infants born in singleton pregnancies and 90,887 infants born in multifetal pregnancies in Japan (> or =22 weeks) over the 5-year period 1989-1993. An estimate of the risk of birth within 1 week at gestational week n was obtained by dividing the number of infants delivered at gestational week n by the number of infants delivered at or beyond gestational week n. The risk at 22 weeks was 0.9 per 1000 fetuses for singleton pregnancies and 5.0 per 1000 for multifetal pregnancies. The risk remained relatively stable until 27 weeks of gestation, then sharply increased toward 36 weeks of gestation in both singleton and multifetal pregnancies. The odds ratio for birth within 1 week for fetuses of multifetal pregnancies compared with fetuses of singleton pregnancies was 5.9 (95% CI, 5.4-6.5) at 22 weeks of gestation, increasing gradually with increasing gestational age until 33 weeks of gestation (13.7; 95% CI, 13.1-14.2) but declining thereafter to 8.8 (95% CI, 8.6-8.9) at 36 weeks of gestation. Results of data analysis for each year of the 5-year period did not differ substantially.

Changes in Polymorphonuclear Leukocytes in the Vagina of Patients with Preterm Labor

To evaluate changes in vaginal polymorphonuclear leukocytes (vPMNL) in patients with preterm labor, we obtained vPMNL-rich suspensions from vaginal fluids of 77 women (21 with preterm labor and 56 control women with uncomplicated pregnancy). Total counts of vPMNL and % viability of vPMNL (viable vPMNL:total vPMNL) were significantly higher in patients with preterm labor (37 ± 92 × 105, 23 ± 29%) vs. controls (11 ± 15 × 105, 6.9 ± 8.3%). The concentration of granulocyte elastase in vaginal fluid diluted to 20 ml was also higher in patients with preterm labor than in controls (4,806 ± 3,818 vs. 2,739 ± 2,556 ng/ml). We conclude that PMNL and granulocyte elastase are abundant in the vagina in patients with preterm labor, which suggests that the PMNL may be involved in the pathogenesis of preterm labor.

Stimulated Polymorphonuclear Leukocytes in Vaginal Secretions from Patients with Preterm Labor

The purpose of this study was to examine evidence for the presence of activated vaginal leukocytes in women with preterm labor. Vaginal polymorphonuclear leukocytes from 7 patients in preterm labor (24–32 weeks of gestation) as well as from 7 control women with uncomplicated pregnancy were analyzed morphologically using transmission electron microscopy. Peroxidase and NADPH oxidase cytochemistry was also performed. Viable leukocytes were abundant in patients in preterm labor. Phagosomes, phagocytosis of bacteria, attachment of primary granules to the phagosomal membrane, and cell surface projections were observed in the vaginal leukocytes but not in the peripheral blood leukocytes. Peroxidase activity was visible on the cell surface, the phagosomal membrane, and the primary granules. NADPH oxidase activity was demonstrated on the cell surface of leukocytes. Morphological and cytochemical features indicated that vaginal polymorphonuclear leukocytes were stimulated in situ. Such stimulated leukocytes may play a role in the pathogenesis or pathophysiology of preterm labor.

Relation between hemoglobin discordance and adverse outcome in monochorionic twins.

BACKGROUND The effects of discrepancies in the birth weight and hemoglobin concentration ([Hb]) at the birth on infant outcome have not been fully investigated in monochorionic (MC) and dichorionic (DC) twins. METHODS A retrospective study of 95 twin pregnancies. All 190 neonates (68 MC twins and 122 DC twins) were admitted to the neonatal intensive care unit, and the [Hb] was determined soon after birth. The [Hb] discordance represents the [Hb] of the smaller twin expressed as a percentage of the [Hb] of the larger twin. Infants were followed-up until 1 year of corrected age and their psychomotor development was evaluated between 12 and 18 months. RESULTS One DC infant died by 1 year of age. Twelve MC infants and eight DC infants had disabilities by 1.5 year of age. In the MC group, 11 infants (28%) of 20 pairs with an intertwin [Hb] discordance >100 had disabilities compared with one (3.6%) of 14 pairs with an [Hb] discordance < or = 100 (p<0.05). A similar trend was observed in the DC group, but the difference was not significant. The incidence of disabled infants increased as the intertwin birth weight discordance increased in MC twins. CONCLUSIONS An adverse outcome at 1 year of age in MC twins was associated with a greater birth weight discordance and an [Hb] disordance that indicated polycythemia in the smaller twin.