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Introduction Some pregnant women develop significant proteinuria in the absence of hypertension. However, clinical significance of isolated gestational proteinuria (IGP) is not well understood. This study aimed to determine the prevalence of IGP in singleton pregnancies and the proportion of women with IGP who subsequently developed preeclampsia (IGP-PE) among all PE cases. Material and methods This was an observational study of 6819 women with singleton pregnancies at 12 centers, including 938 women with at least once determination of protein-to-creatinine ratio (P/Cr). Significant proteinuria in pregnancy (SPIP) was defined as P/Cr (mg/mg) level >0.27. IGP was defined as SPIP in the absence of hypertension. Gestational hypertension (GH) preceding preeclampsia (GH-PE) was defined as preeclampsia (PE) in which GH preceded SPIP. Simultaneous PE (S-PE) was defined as PE in which both SPIP and hypertension occurred simultaneously. Results IGP and PE were diagnosed in 130 (1.9%) and 158 (2.3%) of 6819 women, respectively. Of 130 women with IGP, 32 (25%) progressed to PE and accounted for 20% of all women with PE. Hence, women with IGP had a relative risk of 13.1 (95% CI; 9.2–18.5) for developing PE compared with those without IGP [25% (32/130) vs. 1.9% (126/6689)]. At diagnosis of SPIP, P/Cr levels already exceeded 1.0 more often in women with S-PE than in those with IGP-PE [67% (33/49) vs. 44% (14/32), respectively, p = 0.031]. Conclusions IGP is a risk factor for PE, and IGP-PE accounts for a considerable proportion (20%) of all PE.

Our aim was to clarify the perinatal outcomes of and risk factors for hypertension that is first detected after labor onset (labor onset hypertension, LOH), which may be a risk factor for eclampsia and stroke during labor. A total of 1349 parturient women who did not exhibit preeclampsia or gestational hypertension prior to labor were examined. The patients were classified into four groups: the normotensive (n=1023) (whose systolic blood pressure (SBP) remained below 140 mm Hg throughout labor), mild LOH (n=241) (whose maximum SBP during labor ranged from 140 to 159 mm Hg), severe LOH (n=66) (whose maximum SBP during labor ranged from 160 to 179 mm Hg) and emergent LOH groups (n=19) (whose maximum SBP during labor was greater than 180 mm Hg). The perinatal outcomes and patient characteristics of the four groups were compared. Twenty-four percent of the pregnant women who remained normotensive throughout pregnancy developed hypertension during labor. One of the patients in the emergent LOH group developed eclampsia. The blood pressure at delivery and frequencies of hypotensor use, interventional delivery and low Apgar scores differed significantly among the four groups. The following risk factors for severe/emergent LOH were extracted: being over 35 years old, a body mass index at delivery of >30, an SBP at 36 weeks' gestation of 130-134 mm Hg, an SBP at admission of 130-139 mm Hg, proteinuria (a score of 2+ on the dipstick test) and severe edema. The risk factors for severe/emergent LOH were identified in this study. In high risk cases, repeatedly measuring maternal blood pressure during delivery might help detect critical hypertension early.

Eclampsia and stroke during pregnancy are major causes of maternal and neonatal death in many countries. Herein, we describe the etiologies of and therapeutic strategies for eclampsia and stroke during pregnancy.

Aim The aim of this study was to analyze the causes and outcomes for intracerebral hemorrhage (ICH) occurring during pregnancy and postnatally. Material and Methods A nationwide study of pregnancy-related ICH in Japan was performed. We contacted 1582 facilities to identify women with ICH in pregnancy or postnatally between 1 January 2006 and 31 December 2006. A total of 1012 facilities (70%) responded with completed questionnaires. Risk factors for ICH, neurological features, onset to diagnosis time (O–D time), and obstetric data were recorded. Results Thirty-eight cases of pregnancy-associated ICH were identified, corresponding to 3.5 per 100 000 deliveries. There were seven maternal deaths, giving a case mortality rate of 18.4%. Pre-eclampsia was identified in 10 cases (26.3%) and hemolysis elevated liver enzymes and low platelet count (HELLP) syndrome was present in five. There were four cases (10.5%) with Moyamoya disease and seven (18.4%) with arteriovenous malformation. HELLP syndrome and moderately or severely disturbed consciousness at disease onset were significantly associated with a poor outcome (modified Rankin Scale ≥3). Pre-eclampsia, HELLP syndrome and O–D time >3 h were significantly associated with maternal mortality. Conclusion Early diagnosis may prevent maternal death, even in severe cases of pregnancy-related ICH. However, maternal–fetal care centers do not always have full-time neurosurgeons or diagnostic imaging tools suitable for diagnosis of ICH. Thus, a network should be established between maternity centers and neurosurgery departments with computed tomography or magnetic resonance imaging available at all times. We recommend transferal of pregnant women with neurological symptoms to a regional facility that is equipped to treat such patients.

Introduction Eclampsia and stroke during pregnancy are major causes of maternal death in the world. We have experienced cases in which pregnant women developed hypertension firstly after the onset of labor (labor onset hypertension; LOH). While they might be the risk for eclampsia and stroke during labor, their detail pathophysiology has not been well examined. Objective Our aim is to clarify the perinatal outcomes of and risk factors for LOH. Methods A total of 1349 parturient women that did not exhibit preeclampsia or gestational hypertension prior to labor were examined. The patients were classified into 4 groups, the normotensive (n = 1023) (whose systolic blood pressure (SBP) remained below 140 mmHg throughout labor), mild LOH (n = 241) (whose maximum SBP during labor ranged from 140 to 159 mmHg), severe LOH (n = 66) (whose maximum SBP during labor ranged from 160 to 179 mmHg), and emergent LOH groups (n = 19) (whose maximum SBP during labor was greater than 180 mmHg). The perinatal outcomes and patient characteristics of the 4 groups were compared. Results Twenty-four percent of the pregnant women who remained normotensive throughout pregnancy developed hypertension during labor. One of the patients in the emergent LOH group developed eclampsia. Blood pressure at delivery and the frequencies of hypotensor use, interventional delivery, and low Apgar scores differed significantly among the 4 groups. The following risk factors for severe/emergent LOH were extracted: being aged more than 35 years, a body mass index at delivery of >30, an SBP at 36 weeks’ gestation of 130–134 mmHg, an SBP at admission of 130–139 mmHg, proteinuria, and severe edema. Discussion The risk factors for severe/emergent LOH were identified in this study. In high risk cases, repeatedly measuring maternal blood pressure during delivery might help to detect critical hypertension early. LOH might be a novel category among hypertensive disorders of pregnancy.

Background: The dipstick test is widely used as a primary screening test for detection of significant proteinuria in pregnancy (SPIP). However, it often shows a false positive test result. This study was performed to determine which pregnant women should be recommended to undergo determination of urinary protein-to-creatinine ratio (mg/mg, P/Cr test) after dipstick test for confirmation of SPIP. Methods: This was a multicenter, prospective, and observational study of 2212 urine specimens from 1033 pregnant women who underwent simultaneous dipstick and P/Cr tests in the same spot urine samples at least once. SPIP was defined as P/Cr > 0.27. Preeclampsia was diagnosed in women with both hypertension and SPIP. Results: Preeclampsia, hypertension alone, and SPIP alone developed in 202 (20 %), 73 (7.1 %), and 120 (12 %) women, respectively. Creatinine concentration [Cr] varied greatly, ranging from 8.1 to 831 mg/dL in the 2212 urine samples. Rate of positive dipstick test results increased with increasing [Cr], while SPIP prevalence rate was lower in urine samples with higher [Cr], yielding higher false positive rates in samples with higher [Cr]. Postpartum urine samples had significantly lower [Cr] compared to those obtained antepartum (60 [8.7-297] vs. 100 [10-401] mg/dL, respectively). At the first P/Cr test among women with similar dipstick test results, the risk of having SPIP was consistently and significantly higher for hypertensive women than for normotensive women at any dipstick test result: 18 % (14/77) vs. 3.2 % (8/251), 47 % (26/55) vs. 8.7 % (37/425), 91 % (82/90) vs. 59 % (44/75) for negative/equivocal, 1+, and >= 2+ test results, respectively. The risk of SPIP was 16 % (9/55) for normotensive women when two successive antenatal urine samples showed a dipstick test result of 1 +. Conclusions: For prediction of SPIP, the dipstick test was more likely to show a false positive result in concentrated urine samples with higher [Cr]. Hypertensive women with >= 1+ as well as normotensive women with >= 2+ on dipstick test should be advised to undergo the P/Cr test.

Background: To clarify the effect of estradiol benzoate on placental structure and its consequences for fetal survival and fetoplacental growth. Study design: Estradiol benzoate (0, 0.1, 1, 10, 100 μg/day) was infused intraperitoneally into pregnant Wistar rats from 12 to 19 days' gestation. Survival rate, weight of pups and placentas at 20 days' gestation, and plasma levels of estrogen and progesterone were measured. Pathological changes in the placenta were also examined. Results: Estradiol benzoate reduced fetal survival (1 μg/day: 100%, 10 μg/day: 70%, 100 μg/day: 14.6%) and the weights of the pups and placentas in a dose-dependent manner. Maternal estradiol concentration was raised 23-fold with 100μg/day of estradiol benzoate. Trophoblast degeneration, including apoptosis and destruction of placental labyrinth was induced but the structures of the maternal kidney and liver were not affected. Conclusions: In pregnant rats, estradiol benzoate causes fetal mortality at a pharmacological dose (more than 10 μg/day) and fetoplacental growth retardation via trophoblastic degeneration and destruction of the placental labyrinth even at a physiological dose (1 μg/day).

1Department of Obstetrics & Gynecology Nara Medical University, 2Nagoya City West Medical Center, 3Osaka City General Hospital, 4Juntendo University, 5Tohoku University, 6Osaka University, 7Japanese Red Cross Katsushika Maternity Hospital, 8Hokkaido University, 9Saitama Medical University, 10Tokyo Medical University Hachioji Medical Center, 11Ohno Ladies’ Clinic, 12Hamamatsu Medical University, 13Nagoya University, 14Hirosaki University, 15Aichi Medical University

Local concentrations of the vasopressor peptide, angiotensin II (Angll), depend upon the balance between synthesis and degradation. Previous studies of blood pressure (BP) regulation have focused primarily on the generation of Angll and its receptors, and less attention has been devoted to angiotensin degradation. Aminopeptidase A (APA, EC 3.4.11.7) is responsible for the N-terminal cleavage of Angll, a hydrolytic event that serves as a rate-limiting step in angiotensin degradation. To evaluate the physiological role of APA, we examined BP homeostasis in APA-deficient mice. We measured basal BP and BP with continuous infusion of Angll in APA mutant mice by tail-cuff method. We also evaluated the development and histology of Angll-targeted organs as well as urine excretion in these mice. Homozygous APA mutant mice were found to have elevated basal systolic BP when compared with heterozygous mutant and wild-type littermate mice. Infusion of Angll led to an enhanced systolic BP response in the APA-deficient mice. Despite the sustained elevation of BP in APA knockout mice, neither their renal and cardiac sizes nor their histological appearances were not different from control mice. Moreover, the volume, osmolality, and electrolyte content of the urine were normal in APA-deficient mice. APA deficiency increased baseline BP and enhanced the hypertensive response to increased levels of AngII. These findings indicate a physiological role for APA in lowering BP and offer novel insight into the mechanisms for developing hypertension.

Background Hypertension complicated with pregnancy is a major cause of maternal and fetal mortality, but its pathophysiology is unclear. Objective To investigate the pressor response to angiotensin II (Ang II) and the involvement of the Ang II degrading protease, aminopeptidase A, in spontaneously hypertensive rats (SHRs). Design Pregnant SHRs and Wistar–Kyoto (WKY) rats were studied. Angiotensin II (200 ng/kg per min) or saline was infused by osmotic pump from day of 15 gestation, and caesarean section was performed at day 20 of gestation. Blood pressure during pregnancy, weight of placentas and pups at caesarean section, and aminopeptidase A activity in placenta and renal cortex were measured. Results Ang II treatment induced increases in blood pressure that were greater in non-pregnant WKY rats than those in pregnant WKY rats, pregnant SHRs, and non-pregnant SHRs. Renal aminopeptidase A activity in SHRs was significantly lower than that in WKY rats. Renal aminopeptidase A activity in pregnant SHRs was significantly greater than that in non-pregnant SHRs, but there was no significant increase in pregnant WKY rats. Placental aminopeptidase A activity in SHRs was greater than that in WKY rats. Placental aminopeptidase A activity in WKY rats was increased by Ang II, but was not increased in SHRs. Weights of placentas and pups were significantly lower in SHRs than in WKY rats. Conclusions Renal aminopeptidase A may be involved in the development of hypertension and the regulation of blood pressure in SHRs. Placental aminopeptidase A may be upregulated in response to fetal stress in pregnant SHRs.

Diaphragmatic eventration is a rare abnormality, which has the similar ultrasonographic features to congenital diaphragmatic hernia. Therefore, these two diseases are difficult to differentiate from each other prenatally. We present here a case in which the presence of congenital diaphragmatic eventration was strongly suggested by magnetic resonance imaging (MRI) and ultrasonography. A 26-year-old pregnancy woman, gravida 0, para 0, week 35, was admitted to our hospital with an ultrasonographic abnormality of the fetal thorax. MRI and ultrasonography showed interesting features which strongly suggested the presence of congenital diaphragmatic eventration and helped to differentiate it from congenital diaphragmatic hernia.

Achalasia is rare motor disorder of esophageal smooth muscle. It has been linked to malnutrition during pregnancy leading to maternal and fetal mortality. We report a case of achalasia with intrauterine fetal death who succeeded in following pregnancy with good fetal and maternal outcome after operative treatment. A 34-year-old pregnant woman had intrauterine fetal death at 27 gestational weeks due to severe and persistent maternal malnutrition during pregnancy. Achalasia was diagnosed postpartum and myotomy-fundoplasty was performed. She succeeded in normal delivery with a healthy baby 21 months after the operation. This case suggests the effect of severe achalasia of early onset on poor fetal outcome, and the efficacy of surgical myotomy for the improvement of following pregnant outcome.

We report a case of a right ovarian tumor measuring 10.8 × 10 × 8.5 cm (diagnosed as a yolk sac tumor) in a 31-year-old nulligravid woman with serum α-fetoprotein (AFP) level of 25 000 ng/ml and pleural effusion. Seven courses of primary chemotherapy (PVB; cisplatin, vinblastine, bleomycin) were given from May 16 to November 11, 1994. No surgical procedures were conducted. After the second course of PVB, the pleural effusion resolved; after the third course, the tumor disappeared, and after the fourth course, serum AFP decreased to the normal range. At the true of writing (May 11, 1998), the patient is in good health without recurrence, with an AFP level below 20 ng/ml. This paper reports, for the first time, a patient with yolk sac tumor in whom remission was achieved by primary chemotherapy alone.

The 'Clinical Guidelines for Obstetrical Practice, 2011 edition' were revised and published as a 2014 edition (in Japanese) in April 2014 by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction of burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. The number of Clinical Questions and Answers items increased from 87 in the 2011 edition to 104 in the 2014 edition. The Japanese 2014 version included a Discussion, a List of References, and some Tables and Figures following the Answers to the 104 Clinical Questions; these additional sections covered common problems and questions encountered in obstetrical practice, helping Japanese readers to achieve a comprehensive understanding. Each answer with a recommendation level of A, B or C was prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' was weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 104 Clinical Questions and Answers items, with the omission of the Discussion, List of References, and Tables and Figures, are presented herein to promote a better understanding among English readers of the current standard care practices for pregnant women in Japan.

To establish the etiologies and therapeutic strategies for the treatment of eclampsia and stroke during pregnancy, we performed a questionnaire-based study of stroke during pregnancy in Aichi prefecture (2005-2009). This study revealed the following findings: 66% of deliveries were managed in primary medical institutions, 40% of eclampsia episodes and 31% of strokes occurred at primary medical institutions, and 19% of strokes occurred at home. Home-onset strokes displayed a mortality rate of 40%. Using the results of this questionnaire, we investigated cases of eclampsia and/or stroke during pregnancy and revealed important issues regarding their management. In pregnant women with eclampsia or stroke, accurate antihypertensive and anticonvulsive treatment are necessary. Discriminating between eclampsia and stroke during labor is difficult. However, when facial or arm muscle weakness or a facial deficit is detected, stroke should be strongly suspected. Brain computed tomography can usually detect most cases of hemorrhagic stroke. When a stroke is detected, collaborative treatment with a neurosurgeon should be started as soon as possible. If stroke is suspected at a primary medical institution, rapid maternal transport to an intensive medical institution is necessary. In patients whose blood pressure is greater than 180/120 mmHg, the use of MgSO4 to decrease the risk of convulsions and reduce blood pressure is recommended. These findings might aid the development of therapeutic strategies for pregnant women with eclampsia or stroke.

This report describes FHR patterns of monozygotic twins, one of whom was anencephalic. The recording were made from 20 to 36 weeks of gestation. Differences were observed in the FHR patterns after week 28.

Background Cerebral circulatory changes in preeclampsia are unclear. We studied the changes in intracranial blood flow volume using a new color Doppler ultrasonographic assessment in a preeclamptic woman with photophobia. Case A 39-year-old preeclamptic primigravida was admitted and delivered by cesarean at 36 weeks’ gestation. She developed bilateral photophobia with blood pressure elevation at 2 days postpartum. Blood flow volume index {mean velocity × πd2/4} (d = luminal diameter at systolic phase) was established. The sum of blood flow volume indexes of the bilateral internal carotid arteries and vertebral arteries increased at the onset of photophobia and blood pressure elevation. The blood flow volume index increased above 120 mm Hg of mean arterial blood pressure. Conclusion These data represent the increased cerebral hemodynamic changes in preeclampsia with photophobia.

The aim of this study was to analyze the causes and outcomes for intracerebral hemorrhage (ICH) occurring during pregnancy and postnatally.A nationwide study of pregnancy-related ICH in Japan was performed. We contacted 1582 facilities to identify women with ICH in pregnancy or postnatally between 1 January 2006 and 31 December 2006. A total of 1012 facilities (70%) responded with completed questionnaires. Risk factors for ICH, neurological features, onset to diagnosis time (O-D time), and obstetric data were recorded.Thirty-eight cases of pregnancy-associated ICH were identified, corresponding to 3.5 per 100 000 deliveries. There were seven maternal deaths, giving a case mortality rate of 18.4%. Pre-eclampsia was identified in 10 cases (26.3%) and hemolysis elevated liver enzymes and low platelet count (HELLP) syndrome was present in five. There were four cases (10.5%) with Moyamoya disease and seven (18.4%) with arteriovenous malformation. HELLP syndrome and moderately or severely disturbed consciousness at disease onset were significantly associated with a poor outcome (modified Rankin Scale ≥3). Pre-eclampsia, HELLP syndrome and O-D time3 h were significantly associated with maternal mortality.Early diagnosis may prevent maternal death, even in severe cases of pregnancy-related ICH. However, maternal-fetal care centers do not always have full-time neurosurgeons or diagnostic imaging tools suitable for diagnosis of ICH. Thus, a network should be established between maternity centers and neurosurgery departments with computed tomography or magnetic resonance imaging available at all times. We recommend transferal of pregnant women with neurological symptoms to a regional facility that is equipped to treat such patients.

We reported the ophthalmic arterial velocimetry and the effect of prostaglandin E1 on that using color Doppler ultrasonography in a 29-year-old pre-eclamptic woman with postpartum weakness of vision due to retinal arterial narrowing. In this case, we found higher pulsatility index and lower mean velocity than that in normal pregnancy. The 30.8% reduction of ophthalmic artery pulsatility index and 53.9% acceleration of mean velocity were observed at 25 min after intravenous administration of prostaglandin E1. Normalization of these values preceded the recovery of vision. These findings suggest a vasodilated effect of prostaglandin E1 on orbital circulation in a pre-eclamptic woman with weakness of vision due to retinal arterial narrowing.

Background: Cloacal anomalies are rare abnormalities with highly variable forms, which makes them difficult to diagnose antenatally. We present a cloacal anomaly case with interesting antenatal ultrasonographic findings. Case: A 24-year-old woman, gravida 1, para 0, presented at 23 weeks’ gestation with ultrasonographic evidence of fetal ascites. Between 23 and 30 weeks’ gestation, serial ultrasounds showed changing features of a cloacal anomaly, consisting of fetal ascites, a cystic pelvic mass, hydronephrosis, and oligohydramnios. Conclusion: Serial antenatal ultrasound helped diagnose changing features of a cloacal anomaly in our case, thus allowing directed antenatal counseling and appropriate perinatal treatment.

Objective: To compare ophthalmic arterial velocimetry in normotensive and preeclamptic gravidas with and without photophobia. Methods: Ophthalmic arteries were studied by color-flow Doppler ultrasonography in 118 normotensive pregnant women, 20 gravidas with preeclampsia and no visual symptoms, and 11 with preeclampsia, photophobia, and retinal edema. Results: The ophthalmic arterial pulsatility index (PI) correlated negatively with gestational age (y = −0.01x + 1.84, r = −0.41, P < .01). Pulsatility index in preeclamptics with photophobia (0.71 ± 0.17) was lowest among the three groups (P < .01) and was highest in normotensive pregnant women (1.41 ± 0.21, P < .01). Mean velocity in normotensive pregnant women (0.19 ± 0.05 m/second) was highest among the groups (P < .01) and was not significantly different in preeclamptic women with no visual symptoms (0.27 ± 0.03 m/second) and with photophobia (0.30 ± 0.02 m/second). Conclusion: Preeclamptic women, especially those with photophobia, have orbital vascular vasodilation or hyperperfusion, or both.

Glucose transporter 4 (GLUT4) is the main insulin-responsive glucose transporter in skeletal muscle and adipose tissue of human and rodent, and is translocated to the plasma membrane in response to insulin. GLUT2 is well known as the main glucose transporter in pancreatic islets and could highly regulate glucose-stimulated insulin secretion by B-cells as a glucose sensor. We confirmed the presence of GLUT4 mRNA and GLUT4 protein in pancreas in the human. Indirect immunohistochemistry showed that the pancreatic islets of human and rat were conspicuously labeled by anti-GLUT4 antibody. The presence of placental leucine aminopeptidase (P-LAP), a homologue of insulin-regulated aminopeptidase (IRAP), was also shown in the human pancreatic islet. IRAP/P-LAP is thought to be involved in glucose metabolism. This study provides the first evidence that GLUT4 is present in human and rat pancreatic islets and may suggest its specific role in glucose homeostasis in conjunction with IRAP/P-LAP.

Local concentrations of the vasopressor peptide, angiotensin II (AngII), depend upon the balance between synthesis and degradation. Previous studies of blood pressure (BP) regulation have focused primarily on the generation of AngII and its receptors, and less attention has been devoted to angiotensin degradation. Aminopeptidase A (APA, EC 3.4.11.7) is responsible for the N-terminal cleavage of AngII, a hydrolytic event that serves as a rate-limiting step in angiotensin degradation. To evaluate the physiological role of APA, we examined BP homeostasis in APA-deficient mice. We measured basal BP and BP with continuous infusion of AngII in APA mutant mice by tail-cuff method. We also evaluated the development and histology of AngII-targeted organs as well as urine excretion in these mice. Homozygous APA mutant mice were found to have elevated basal systolic BP when compared with heterozygous mutant and wild-type littermate mice. Infusion of AngII led to an enhanced systolic BP response in the APA-deficient mice. Despite the sustained elevation of BP in APA knockout mice, neither their renal and cardiac sizes nor their histological appearances were not different from control mice. Moreover, the volume, osmolality, and electrolyte content of the urine were normal in APA-deficient mice. APA deficiency increased baseline BP and enhanced the hypertensive response to increased levels of AngII. These findings indicate a physiological role for APA in lowering BP and offer novel insight into the mechanisms for developing hypertension.

The purpose of this study was to elucidate the mechanisms underlying the regulation of feto-placental circulation mediated by the renin-angiotensin system under preeclamptic conditions. We measured angiotensin-converting enzyme (ACE) activity, protein expression, and mRNA expression in uncomplicated and preeclamptic placentas and examined the localization of ACE. In addition, ACE activity and mRNA expression in human umbilical venous endothelial cells (HUVECs) under hypoxic conditions were analyzed. ACE activity, protein expression, and mRNA expression in placental tissues from preeclampsia were all significantly higher than those from uncomplicated pregnancies. ACE activity in vessel fractions was extensively higher than that in trophoblast-rich or macrophage-rich fractions. Additionally, ACE activity in HUVECs was significantly higher than that in human arterial endothelial cells, and ACE mRNA was primarily localized to venous endothelial cells of stem villous in placentas. Furthermore, hypoxic condition induced both ACE activity and mRNA expression in HUVECs. These results suggested that venous endothelial cells within placental stem villous tissues and umbilicus play an important role in the regulation of the feto-placental renin-angiotensin system, and in response to hypoxic conditions the feto-placental unit seemed to induce ACE activity in the placenta; such an effect would be likely to lead to regulation of the fetal circulation.

Objective: To test the applicability of maternal serum placental leucine aminopeptidase (P-LAP) as a parameter for predicting preterm delivery. Patients and Methods: Maternal serum P-LAP activity of 61 consecutive women with preterm labor at admission were assayed and examined to assess the relationship of levels to the incidence of preterm and term deliveries. Results: When P-LAP activity of study patient serum was at or below the 10th percentile, we found a greater ratio of preterm delivery (P=0.0085) and an approximately 2.3-fold increase risk. The sensitivity, specificity, positive predictive value and negative predictive value were 29, 97, 89 and 62%, respectively. Conclusion: Maternal serum P-LAP activity decreases in cases with spontaneous preterm delivery and may be a clinically potential marker for some cases of preterm labor.

To clarify the cerebral hemodynamics in pre-eclamptic pregnant women, we investigated the blood flow velocity of the cerebral arteries.The mean blood flow velocity and pulsatility index (PI) of the middle cerebral artery (MCA) and internal carotid artery (ICA) in normal pregnant women (n = 35) and pre-eclamptic patients (n = 18) were examined transcranially using pulsed-wave Doppler technique with a 2 MHz probe. In two pre-eclamptic women with post-partum visual disturbance, we examined the mean blood flow velocity and PI of the MCA and ICA every day.The mean blood flow velocity of the MCA in the pre-eclamptic patients (89.7 +/- 20.5 cm/s) was significantly higher than that in the normal pregnant women (53.6 +/- 16.9 cm/s) (p0.05). PI of the MCA in the former group (0.67 +/- 0.13) was significantly lower than that in the latter (0.78 +/- 0.02) (p0.05). There was no significant difference between these two groups in these variables of the ICA. In the two patients with visual disturbance, the mean blood flow velocity of the MCA was increased before the onset of visual disturbance and decreased gradually following the disappearance of this symptom. In these patients, spasm of the MCA was confirmed by magnetic resonance angiography.In pre-eclamptic patients, we found increased MCA mean velocity before the onset of visual disturbance. Transcranial Doppler may be useful for the evaluation of cerebral hemodynamics and the prediction of eclampsia.

The hydrolysis of bradykinin (BK) by human placental subcellular fractions and pregnancy sera was studied in the presence of inhibitors by measuring amino acids liberated from BK by high-performance liquid chromatography. The effects of the inhibitors DL-2- mercaptomethyl-3-guanidinoethylthiopropionic acid (MGTA, for kininase I), phosphoramidon (for endopeptidase 24.11) and captopril and rentiapril (for angiotensin-converting enzyme [ACE, kininase II]) suggested the essential roles of the above three proteases in BK degradation: among the three proteases, kininase I and endopeptidase 24.11 appeared to be the most important in kininase action in the placenta microsomes, whereas kininase I and ACE appeared to be the most important in kininase action in the placental cytosol, lysosome and pregnancy serum. Measurements of BK concentrations in the umbilical arterial blood, umbilical venous blood and maternal plasma revealed higher concentrations in the mother than in the fetus. The present data suggest that degradation of BK in the placenta and pregnancy serum might contribute to the gradient of BK between mother and fetus.

Fetal behavior in monozygotic twins, one being anencephalic, was serially recorded from 20 to 35 weeks of gestation and analyzed. The commencement of breathing movement was concluded to reflect the development of the medulla oblongata of the fetus.

To measure the umbilical plasma concentration of endothelin (ET)-1 in the presence of labor, fetal heart rate (FHR) abnormalities, and fetal hypoxia.Umbilical and maternal plasma concentrations of ET-1 were measured in 100 pregnant women at full-term deliveries (60 with vaginal delivery without induction and 40 with elective cesarean delivery without labor). We assessed the FHR pattern, measured umbilical blood gases and plasma concentration of vasopressin, and investigated the relationships between the umbilical vein-artery ET-1 concentration difference and these variables.The concentration of ET-1 in the umbilical vein was higher than in the umbilical artery and the maternal vein in all cases. The umbilical vein-artery ET-1 concentration difference (mean +/- standard error of the mean) was significantly greater in the vaginal delivery group (4.5 +/- 2.0 pmol/L) than in those delivered by elective cesarean (1.7 +/- 1.5 pmol/L) (P.05). The umbilical vein-artery ET-1 concentration difference was significantly greater when more than three episodes of severe variable decelerations occurred during the 30-minute period before delivery (7.0 +/- 2.0 pmol/L) than in the absence of any decelerations (1.6 +/- 1.5 pmol/L) (P.05). The umbilical vein-artery ET-1 concentration difference correlated positively with the umbilical arterial concentration of vasopressin (r = 0.45, P.05) and negatively with the umbilical arterial oxygen pressure (r = -0.47, P.05).In cases of vaginal delivery with FHR abnormalities and with fetal hypoxia, the fetoplacental concentration of ET-1 was increased.

Background To our knowledge, there has been no report on longitudinal monitoring of fetal behavior in the anencephalic fetus. Case A 30-year-old woman was diagnosed with a twin pregnancy at 8 weeks' gestation; at week 20, one of the twins was identified as anencephalic. From 25–36 weeks' gestation, the behavioral patterns of each fetus were recorded weekly on videotape for 60 minutes, then compared with morphologic findings after birth. Conclusion Our data comparing normal and anencephalic fetuses indicate that the development of the central nervous system above the medulla oblongata plays an important role in the elimination of fetal movements, such as startle, jumping, and writhing, and in the commencement of breathing movements.

Ohno Y, Kasugai M, Kurauchi O, Mizutani S, Tomoda Y. Effect of interleukin 2 on the production of progesterone and prostaglandin E2 in human fetal membranes and its consequences for preterm uterine contractions. Eur J Endocrinol 1994;130:478–84. ISSN 0804–4643 Our objective was to clarify the mechanism of uterine contraction induced in pregnant women by intrauterine bacterial infection. The concentration of interleukin 2 (IL-2) was measured in amniotic fluids that had been obtained by amniocentesis, transvaginal amniotomy or by transuterine amniocentesis performed at cesarean section in 50 pregnant women. The concentration of IL-2 in those cases with intrauterine infection was significantly higher than that of those without intrauterine infection at preterm. The same tendency was found at term. Scatchard analysis demonstrated the presence of an IL-2 receptor in the fetal membranes. We collected the fetal membranes aseptically for the measurement of progesterone and prostaglandin E2 by radioimmunoassay following incubation with various concentrations of Interleukin I (IL-1) and IL-2 at 37°C for 16 h. The production of progesterone was inhibited significantly by 10 pmol/l IL-2 but not by 10 pmol/l IL-1. The production of prostaglandin E2 was accelerated significantly by either IL-1 or IL-2 at a dose of 10 pmol/l. The inhibitory effect of IL-2 on the production of progesterone was unaffected by indomethacin, which inhibits the production of arachidonate cycloxygenase metabolites such as prostaglandin E2. Our present data suggest that the presence of intrauterine bacterial infection may stimulate the intrauterine production of IL-2, and that the stimulation of IL-2 and the reduction of progesterone caused by IL-2 may in part explain the mechanism of uterine contraction associated with intrauterine infection during pregnancy. Yasumasa Ohno, Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan

To evaluate the efficiency of the Doppler examination of umbilical arterial blood flow for the antenatal diagnosis and the monitoring of fetal condition during intrauterine treatment of twin-to-twin transfusion syndrome (TTTS), we studied 33 pairs of twins including 5 TTTS cases. In all cases umbilical arterial blood flow was examined by Doppler ultrasound and pulsatility index (PI) was calculated as umbilical arterial impedance. In twins with TTTS, PI of the recipient was outside the normal range and the difference of PI was greater than +0.5. In discordant twins without TTTS and concordant twins, the PI was within the normal range and the difference of PI ranged from −0.5 to +0.5. In 2 cases these findings were found before the appearance of fetal hydrops. In 2 TTTS cases transmaternal digitalization prevented the development of hydrops in the recipient. The difference of PI decreased with improvement in the fetal condition, and vice versa. Our data suggested that, in cases with TTTS, Doppler examination of umbilical arterial blood flow was effective in predicting fetal hydrops. Doppler was also very useful for monitoring the fetal condition during intrauterine treatment.

Pure red cell aplasia during pregnancy is rare. We present a case in a 26-year-old pregnant woman, referred to our hospital at 31 weeks’ gestation because of severe anemia caused by acute hepatitis. She was treated with repeated blood transfusions and the pure red cell aplasia gradually remitted during the pregnancy. A live infant was delivered by cesarean section at 34 weeks’ gestation. Postpartum, the pure red cell aplasia and hemolytic anemia remitted completely. Our case illustrates that pure red cell aplasia may occur late in pregnancy associated with acute viral hepatitis and is reversible during pregnancy without any necessity for steroid therapy.

To elucidate whether breast milk, vaginal discharge and contamination with maternal blood at birth are possible routes of mother-to-child transmission of hepatitis C virus (HCV), we examined HCV RNA in the cord and peripheral blood of infants, and in the blood, vaginal discharge, and breast milk of anti-HCV seropositive mothers. From July 1991 to July 1992, we studied 20 healthy pregnant women, who were seropositive with the Ortho anti-HCV EIA, and their infants. Using a sensitive nested polymerase chain reaction (nested PCR), we investigated the presence or absence of hepatitis C virus in the above-mentioned specimens. Moderate elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was observed in only one woman in the first and third trimesters. The nested PCR and subsequent Southern hybridization detected 0.5–5.5 copies of HCV c-DNA. HCV RNA was detected in 17/20 blood samples (85%), 7/14 vaginal discharge samples (50%) and 4/10 cord blood samples (40%). However, no HCV RNA was identified in the peripheral blood of infants or breast milk. The mother-to-child transmission of HCV at delivery or via breast milk does not appear to contribute much to maintaining the global HCV reservoir.