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Sirenomelia is a rare congenital malformation characterized by varying degrees of fusion of the lower extremities. It is commonly associated with severe urogenital and gastrointestinal malformations; however, the association of sirenomelia with anencephaly and rachischisis totalis is extremely rare. To our knowledge, the prenatal sonographic images of this association have not been previously published. Here, we present prenatal sonographic images of this association, detected during the 17th week of gestation through combined two-dimensional, four-dimensional, and color Doppler ultrasound. Two-dimensional ultrasound images showed anencephaly, spina bifida, and possible fusion of the lower limbs. Three-dimensional HDlive rendering images confirmed the final diagnosis of sirenomelia with anencephaly and rachischisis totalis. The patient opted to undergo medical termination of pregnancy and delivered a fetus with fused lower limbs, anencephaly, and rachischisis totalis confirming the in utero imaging findings. Awareness of these rare associations will help avoid misdiagnoses and facilitate prenatal counselling. This case highlights the importance of a thorough ultrasound examination. [ABSTRACT FROM AUTHOR]

The mass food poisoning incident yusho occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls and various dioxins and dioxin-like compounds including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). Notably, PCDFs were found to contribute to approximately 65% of the total toxicity equivalent in the blood of yusho patients. Lipophilic dioxins are retained in the body for a longer period than previously estimated. Victims suffered from characteristic skin manifestations associated with non-specific systemic symptoms, neurological symptoms, and respiratory symptoms. The severe symptoms seen in the initial phase subsequently faded, but recently, improvements have scarcely been observed. The Yusho Group has been researching treatments for this condition. Several clinical trials with chelating agents or dietary fibers aimed at accelerating the excretion of compounds. While some treatments increased dioxin excretion, none provided satisfactory symptom relief. Concurrently, various phytochemicals and herbal extracts have been found to possess biological activities that suppress dioxin-induced toxicity via aryl hydrocarbon receptor or activate the antioxidant nuclear factor-erythroid 2-related factor-2 (NRF2) signal pathway, making them promising therapeutic candidates. Here, we summarize the current status of yusho and findings of clinical trials for yusho patients and discuss the treatment prospects. [ABSTRACT FROM AUTHOR]

Aim We conducted a retrospective analysis of summary medical reports of children diagnosed with cerebral palsy (CP) to identify clinical features of antenatal onset of CP secondary to transient ischemia in utero. Methods The 658 brief summary reports available in the Japan Obstetric Compensation System for Cerebral Palsy were screened, and we identified cases of singleton pregnancy, delivered at gestational age ≥ 33 weeks and those with cord blood gas pH ≥ 7.20. Of the 137 cases identified, 84 were excluded for the following reasons: no evidence of ischemic brain lesion, clear post-natal causative factor of CP, presence of a congenital condition, and sentinel hypoxic event, such as uterine rupture. The demographic profiles of the 53 cases included in our analysis were compared to identify those with and without an abnormal variability in fetal heart rate. Results Between-group comparison identified an association between abnormal heart rate variability and a lower Apgar score at 1 min (2 vs 6; P < 0.001) and 5 min (5.5 vs 8; P = 0.002), and more frequent episodes of fetal movement loss (41% vs 10%; P = 0.027). An hypoxic event ≤ 1 week before delivery was more likely to be associated with abnormal heart rate variability (89%) and low Apgar score (82%), while events at > 1 week were associated with development of polyhydramnios (44%). Conclusion In utero transient ischemic events can contribute to term or near-term CP. Careful follow-up is recommended for fetuses with a history of fetal movement loss, abnormal variability in heart rate, and polyhydramnios of unknown causes. [ABSTRACT FROM AUTHOR]

Criss-cross heart is a rare congenital cardiac anomaly characterized by the crossing of two ventricular inflow streams. We have demonstrated the utility of 4-dimensional color Doppler rendering in diagnosing the criss-cross heart in a fetus. Four-dimensional color Doppler rendering can demonstrate the relative direction of intracardiac blood flows and facilitate recognition of the crossover of inflow streams in the same plane, confirming the criss-cross heart diagnosis in the fetus. [ABSTRACT FROM AUTHOR]

Aortic regurgitation in association with aortic stenosis is rare in the fetus. Findings have shown that severe aortic regurgitation is worsened by the increase in systemic vascular resistance after birth, resulting in low cardiac output, hypoxemia, and neonatal death. This report describes a unique case of aortic regurgitation with aortic stenosis, severe mitral regurgitation, retrograde flow in the aortic arch, and an enormous left atrium with a restrictive foramen ovale in a fetus. In this case, aortic regurgitation was diminished immediately after birth, indicating that spontaneous improvement in aortic regurgitation after birth should be taken into account when the final prognosis is predicted. [ABSTRACT FROM AUTHOR]

Aim: Prenatal exposure to dioxins may result in many adverse health effects. However, the mechanisms by which dioxins are transferred from mother to fetus through the placenta are not well understood. The aim of this study was to investigate the differences in dioxin concentrations between maternal blood, the placenta, and cord blood in normal pregnant women, and to identify which individual congeners of these compounds are transferred from mother to fetus through the placenta. Material and Methods: Samples were collected from 19 pregnant Japanese women. Specific congeners of seven polychlorinated dibenzo- p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), and four non- ortho polychlorinated biphenyls (PCBs) were analyzed. Results: The TEQ concentrations of PCDDs, PCDFs, and non- ortho PCBs were 8.03, 3.39, and 3.95 pg TEQ/g lipid, respectively, in the maternal blood; 8.78, 3.61, and 0.87 pg TEQ/g lipid in the placenta; and 4.33, 1.25, 1.08 pg TEQ/g lipid in the cord blood. Among specific congeners, 1,2,3,7,8-PentaCDD and 2,3,4,7,8-PentaCDF exhibited a placenta to maternal blood ratio greater than 1.0, while OctaCDD exhibited the greatest cord blood to placenta ratio. The cord blood to maternal blood ratio of total PCDDs was significantly higher than that of total PCDFs and total non- ortho PCBs. Conclusion: The dioxin concentration in cord blood was approximately half of the amount in maternal blood, despite congeners showing a high toxic equivalency factor accumulating in the placenta. PCDDs were transferred more readily than PCDFs and non- ortho PCBs from maternal blood to the fetus through the placenta. [ABSTRACT FROM AUTHOR]

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, causes reproductive and developmental toxic effects in pups following maternal exposure in a number of animal models. Our previous studies have demonstrated that TCDD imprints sexual immaturity by suppressing the expression of fetal pituitary gonadotropins, the regulators of gonadal steroidogenesis. In the present study, we discovered that all TCDD-produced damage to fetal production of pituitary gonadotropins as well as testicular steroidogenesis can be repaired by co-treating pregnant rats with α-lipoic acid (LA), an obligate co-factor for intermediary metabolism including energy production. While LA also acts as an anti-oxidant, other anti-oxidants; i.e., ascorbic acid, butylated hydroxyanisole and edaravone, failed to exhibit any beneficial effects. Neither wasting syndrome nor CYP1A1 induction in the fetal brain caused through the activation of aryl hydrocarbon receptor (AhR) could be attenuated by LA. These lines of evidence suggest that oxidative stress makes only a minor contribution to the TCDD-induced disorder of fetal steroidogenesis, and LA has a restorative effect by targeting on mechanism(s) other than AhR activation. Following a metabolomic analysis, it was found that TCDD caused a more marked change in the hypothalamus, a pituitary regulator, than in the pituitary itself. Although the components of the tricarboxylic acid cycle and the ATP content of the fetal hypothalamus were significantly changed by TCDD, all these changes were again rectified by exogenous LA. We also provided evidence that the fetal hypothalamic content of endogenous LA is significantly reduced following maternal exposure to TCDD. Thus, the data obtained strongly suggest that TCDD reduces the expression of fetal pituitary gonadotropins to imprint sexual immaturity or disturb development by suppressing the level of LA, one of the key players serving energy production. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in full-term pregnant women leads to fetal or neonatal toxicity. However, the differences in fetal toxicity among NSAIDs remain to be fully investigated. • Therefore, the ability to predict fetal toxicity of NSAIDs quantitatively at full-term pregnancy would be of clinical value. WHAT THIS STUDY ADDS • This study presents a novel approach to predict quantitatively the fetal risk of NSAIDs administered to the mother. • This study shows that the fetal risk of diclofenac is higher than that of salicylic acid and antipyrine using the novel method. • Human placental perfusion study and pharmacokinetic/pharmacodynamic analysis may provide basic data for predicting human fetal toxicity of drugs. AIM The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in full-term pregnant women leads to fetal or neonatal toxicity, such as constriction of the ductus arteriosus (DA) and persistent pulmonary hypertension in the newborn. The aim of this study was to predict quantitatively the fetal toxicity of three NSAIDs (antipyrine, salicylic acid and diclofenac) using the transplacental pharmacokinetic parameters obtained from our previous placental perfusion studies. METHODS Human fetal plasma concentration profile after oral administration of each NSAID to the mother was estimated using the transplacental pharmacokinetic parameters and pharmacokinetic parameters in adult women. The fetal plasma concentration-response relationship for the three NSAIDs was estimated by pharmacokinetic/pharmacodynamic analysis of the results of previous studies investigating the effects of NSAIDs on the ratio of inner diameter of the DA to that of the pulmonary artery (DA/PA) in rats and the plasma concentration profiles of NSAIDs in pregnant rats. RESULTS The risk of constriction of the DA was well predicted by the model. Mean DA/PA ratio after oral administration of diclofenac to the mother was estimated to be 39.0%, whereas both of the corresponding values after oral administration of antipyrine and salicylic acid were estimated to be 5.9%. These results suggest that the fetal risk of diclofenac is higher than those of salicylic acid and antipyrine. CONCLUSIONS This study presents a novel approach to predict quantitatively the fetal risk of NSAIDs administered to the mother. Human placental perfusion study and pharmacokinetic/pharmacodynamic analysis may provide basic data for predicting human fetal toxicity of drugs. [ABSTRACT FROM AUTHOR]

This report describes a case of Ebstein anomaly in a fetus with cardiomegaly, severe tricuspid regurgitation, pulmonary regurgitation, and retrograde ductal flow that showed a marked increase in the size of the right atrium with advancing gestational age. Elective preterm delivery was performed at 35 weeks gestation. The prostaglandin E1 infusion resulted in more pronounced systemic hypotension and acidosis secondary to circular shunt across the patent ductus arteriosus as well as pulmonary regurgitation and tricuspid regurgitation. Emergency surgical intervention consisting of main pulmonary artery ligation, ductus arteriosus ligation, central shunt creation, and plication of the right atrium without cardiopulmonary bypass was performed 4 h after birth. At the age of 16 days, the Starnes procedure was performed. The infant's postoperative course was uneventful. A fetus that has Ebstein anomaly associated with pulmonary regurgitation is at risk for circular shunt across the patent ductus arteriosus after delivery. Planned delivery and surgical intervention without delay after birth are useful for the treatment of such cases. [ABSTRACT FROM AUTHOR]

Pulmonary sequestration is defined as nonfunctional lung tissue that lacks communication with the bronchial tree and that is supplied by an anomalous systemic vessel. In comparatively rare cases, pulmonary sequestration may lead to hydrothorax or hydrops fetalis, which is nearly universally fatal. In this report, we describe a case of pulmonary sequestration with hydrops fetalis, which was successfully treated by thoracoamniotic shunting. A sonographic Doppler study in this case suggested that the underlying mechanism of the hydropic change in a fetus with extralobar pulmonary sequestration may have differed from that in fetuses with primary hydrothorax not associated with a structural anomaly. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011; [ABSTRACT FROM AUTHOR]

BackgroundAbnormal activation and/or dysfunction of the maternal vascular endothelium have been implicated as a cause of the placental ischemia and oxidative damage associated with pregnancy-induced hypertension (PIH).MethodsTo clarify the relationship between systemic oxidative stress and placental damage induced by reactive oxygen species (ROS), we immunostained placentas from 27 PIH pregnancies and 41 normal pregnancies for 8-hydroxy-2-deoxyguanosine (8OHdG).ResultsPositive 8OHdG staining was significantly more frequent in the syncytiotrophoblasts from PIH pregnancies compared to normal pregnancies matched for maternal age/gestational age at delivery. Comparison of 8OHdG positive and negative PIH patients revealed that antenatal serum uric acid (UA) was significantly higher, gestational age at delivery was significantly lower and early onset PIH was more frequent in patients with 8OHdG positive staining in the placenta.ConclusionThese results suggest that ROS directly injures the placental syncytiotrophoblast in PIH patients and that elevated UA in PIH patients, at least partly, indicates placental damage induced by ROS. Moreover, the role and significance of ROS injury in the placenta may differ between early onset and late-onset type PIH.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.40 [ABSTRACT FROM AUTHOR]

Background: Amnioreduction remains a treatment option for pregnancies with twin-to-twin transfusion syndrome (TTTS) not meeting criteria for laser surgery or those in which it is not feasible. Amnioreduction is a relatively simple treatment which does not require sophisticated technical equipment. Previous reports of conservative management have indicated that major neurodevelopmental impairment occurs in 14.3-26% of survivors. The purpose of this study was to investigate long-term neurodevelopmental outcome in conservatively treated TTTS. Methods: During the nine-year study period from January 1996 to December 2004, all pregnancies with TTTS who were admitted to our center were investigated. TTTS was diagnosed by using standard prenatal ultrasound criteria, and staged according to the criteria of Quintero et al. We reviewed gestational age at diagnosis, gestational age at delivery, the stage of TTTS at diagnosis, and diagnosis to delivery interval. Neonatal cranial ultrasound findings were reviewed and the neurodevelopmental outcomes were evaluated. Results: Twenty-one pregnancies with TTTS were included. Thirteen pregnancies (62%) were treated with serial amnioreduction. The mean gestational age at delivery was 28 weeks (22 - 34 weeks). The perinatal mortality rate was 42.9%. Twenty survivors were followed up until at least 3 years of age. The mean age at follow-up was 6.3 years (3 - 12 years). Six children (30%) had neurodevelopmental impairment. Four children (20%) had major neurodevelopmental impairment and two children (10%) had minor neurodevelopmental impairment. Children with neurodevelopmental impairment were delivered before 29 weeks of gestation. Conclusions: Our study showed a high rate of perinatal mortality and a high rate of major neurodevelopmental impairment in conservatively treated TTTS. The long-term outcomes for the survivors with TTTS were good when survivors were delivered after 29 weeks of gestation. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy in the recipient fetus of twin-twin transfusion syndrome (TTTS) has been reported previously. We encountered an unusual set of monochorionic twins in which one twin had cardiac hypertrophy without TTTS while the other fetus had selective growth restriction. In this case, the diagnosis of selective growth restriction was made at 17 weeks of gestation, and right ventricular hypertrophy was identified in the co-twin at 21 weeks; however, no signs of TTTS were observed. At 29 weeks we concluded that the fetal circulation had deteriorated based on echocardiographic findings that included hydrops fetalis and an elevated preload index. Emergency cesarean section was performed. Our experience suggests that hypertrophic cardiomyopathy-like change in a monochorionic twin pregnancy may arise in settings outside of TTTS, including growth restriction of a co-twin. We believe our case will assist the discussion surrounding the etiology of cardiac hypertrophy in monochorionic twins. [ABSTRACT FROM AUTHOR]

Twin-twin transfusion syndrome (TTTS) carries a significant risk of perinatal morbidity and mortality. Serial amnioreduction and fetoscopic laser photocoagulation have decreased perinatal mortality, thereby shifting attention towards short-term and long-term morbidity. Most morbidity occurs within the central nervous system. Ischemic lesions, however, such as congenital skin loss and limb necrosis may occur anywhere in the vasculature of recipient twins. Ischemia may also occur during serial amnioreduction and fetoscopic laser photocoagulation. We report a case of ileal perforation in the donor twin of untreated TTTS. Histopathology showed a focal area of erosion, possibly from ischemia. We also discuss the clinical features of ischemic intestinal complications of TTTS and review the literature. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This report discusses the case of a fetus with previously normal findings of cardiotocograph that experienced an acute neurologic insult antenatally. The fetus presented with abnormalities of its heart rate tracing and its movement patterns on ultrasound. Following delivery, the infant was diagnosed with hypoxic ischemic encephalopathy by DWI in the first 24 h after birth, despite having a normal postnatal brain ultrasound. [ABSTRACT FROM AUTHOR]

Sacrococcygeal teratomas have been diagnosed prenatally on sonograms as masses of cystic, solid, or mixed echogenicity from the sacral area and protruding through the perineum or buttocks. However, a cystic sacrococcygeal teratoma may be misdiagnosed as an anterior sacral meningomyelocele, especially when presenting as a posterior cystic mass. We report a case in which three-dimensional power Doppler imaging was helpful for making a correct prenatal diagnosis of a type 1 cystic sacrococcygeal teratoma, which mimicked a meningomyelocele. [ABSTRACT FROM AUTHOR]

Introduction: Proximal focal femoral deficiency (PFFD) is a rare skeletal disorder characterized by failure in development of the subtrochanteric region of the femoral shaft, with varying degrees of shortening of the proximal femur. Objective: To investigate the potential of helical computed tomography as a prenatal diagnostic tool for bony abnormalities. Case: A 37-year-old Japanese woman was referred to our hospital at 32 weeks of gestation for the evaluation of fetal growth restriction with short femurs. An ultrasound examination revealed the fetus to have short femurs bilaterally with normal echogenicity, and a normal facial profile. Assessment by 3D CT confirmed the absence of the femoral heads bilaterally and also revealed bilateral hip dislocations and oligodactyly of the right hand. The baby was delivered by cesarean section at 37 weeks of gestation, whereupon the diagnosis of PFFD was confirmed. Conclusion: Helical CT is a useful prenatal diagnostic alternative for bony abnormalities that is superior to the conventional sonographic approach. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The natural history of patients with antenatally diagnosed congenital cystic adenomatoid malformation of the lung (CCAM) is still fully unknown. In symptomatic patients with respiratory distress, an operation is performed during the neonatal period. However, in asymptomatic patients, the optimal timing of the operation remains controversial. During the period from 1977 to 2007, we experienced 14 CCAM patients diagnosed antenatally. Therefore, we investigated the outcome of antenatally diagnosed CCAM patients to clarify the optimal treatment for such patients.Methods: Fourteen patients were reviewed regarding the antenatal ultrasonography findings and postnatal clinical course. They were then classified into three groups according to the clinical manifestations. Group A was associated with hydrops fetalis (n = 2), group B had respiratory symptoms just after birth (n = 6), and group C was asymptomatic at birth (n = 6). The postnatal clinical courses in three groups were reviewed.Results: In group A, all two patients with hydrops fetalis died just after birth. In group B, six patients had a severe respiratory distress and underwent operation during the neonatal period. In group C, five out of six patients were asymptomatic and received elective operation during the early infant period. In the remaining one patient, the lesion spontaneously disappeared over time after birth. The mean age at the time of operation in group B and group C was 4.5 days and 4.5 months of age, respectively. In almost all patients in group C, we performed an operation within the first 6 months. During this observation period, we did not experience any complications associated with CCAM.Conclusion: In patients with hydrops fetalis, fetal intervention is thought to be needed. In patients with asymptomatic CCAM, an elective operation during the early infant period is recommended to prevent the risk of complications associated with CCAM before 6 months of age. In addition, we recommend the performance of a partial lung resection using an axillary skin crease incision in order to obtain a good postoperative quality of life. [ABSTRACT FROM AUTHOR]

We describe biochemical assessment of maternal circulation in a case of massive fetomaternal hemorrhage at term associated with intraplacental choriocarcinoma. Markedly elevated maternal serum hCG level at 37 weeks of gestation suggested choriocarcinoma as a cause of fetomaternal hemorrhage in this case. Measurement of maternal hCG may be a useful parameter when intraplacental choriocarcinoma is in the differential diagnosis. In addition, the placenta should be examined in all cases of fetomaternal hemorrhage. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose To investigate the validity of the fetal right lung-to-liver signal intensity ratio (LLSIR) for prediction of postnatal outcomes in left-sided congenital diaphragmatic hernia (CDH) Materials and Methods The study included 14 pregnant women who underwent MR exams for evaluation of fetal left-sided CDH. The fetuses were divided into two groups: Group A (n = 9), alive, and Group B (n = 5), dead. On the basis of the half-Fourier acquisition single-shot turbo spin-echo sequence, LLSIR and the right fetal lung volume (FLV) was calculated. In the control group, a regression analysis was performed to associate LLSIR and right FLV with gestational age. The relative LLSIR and right FLV (the observed/expected LLSIR and right FLV) were compared between Groups A and B. Results The mean relative LLSIR, as well as the mean relative right FLV, of Group A was significantly higher than that of Group B (p = 0.035). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the relative LLSIR and the relative right FLV, when the cutoff point was defined as 0.646 and 0.420, were the same and were 88.9%, 80.0%, 88.9%, 80.0%, and 85.7%, respectively. Conclusion The postnatal outcomes in left-sided CDH may be predicted using the LLSIR. J. Magn. Reson. Imaging 2009;30:112-120. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background/objectives: No definitive treatment strategy has been established for patients with an antenatal diagnosed congenital diaphragmatic hernia (AD-CDH). From 1997 to 2003 in this department fetal stabilization (FS) was administered using both morphine and diazepam via the placenta just before delivery of the fetus by cesarean section. In contrast, from 2004 to the present, a combination of gentle ventilation (GV) and a delayed operation was selected, which was performed when the patient's circulatory stabilization (CS) was achieved.Patients and Methods: This study included 22 patients in the FS group and 16 patients in the GV + CS group, respectively. The outcomes in both groups were compared and the outcome in AD-CDH patients with a patch repaired operation, liver-up or lower lung-to-thorax transverse area ratio (L/T, <0.10) was further investigated in both groups.Results: The overall survival rate (SR) was 93.8% in the GV + CS group and 59.1% in the FS group, respectively (P = 0.04). For the patients with the lower L/T, the SR was 85.7% in GV + CS group and 53.8% in the FS group (P = 0.33). Regarding the patients using a patch and liver-up, the SR in GV + CS group was better than that in the FS group (patch: FS 44.4%, GV +/- CS 87.5%, P = 0.18; liver-up: FS 57.8 and 87.5%, P = 0.30).Conclusion: Our strategy of using GV +/- CS might thus be considered to be more effective than that using FS in the treatment of AD-CDH patients. [ABSTRACT FROM AUTHOR]

Trisomy 16 mosaicism detected at midtrimester amniocentesis is rare and indicative of true fetal mosaicism. We report a case of mosaic trisomy 16 diagnosed by amniocentesis in which the sonographic findings included fetal pulmonary artery stenosis, a single umbilical artery, and early onset fetal growth restriction. The pregnancy was legally terminated. A review of previous reports suggests that abnormalities of outlet tracts are rarely encountered in fetuses with trisomy 16 mosaicism revealed via amniocentesis. [ABSTRACT FROM AUTHOR]

Aims: To identify the clinical characteristics of fetal abdominal wall defects managed at a single institution and to provide information regarding the most likely clinical course of the affected fetuses. Methods: A retrospective review was conducted of 44 fetuses prenatally diagnosed with abdominal wall defects at Kyushu University Hospital between 1990 and 2006. Results: A total of 11 cases of gastroschisis and 33 cases of omphalocele were found. Preterm delivery was observed in eight of 11 fetuses (72.7%) with gastroschisis and in 14 of 27 fetuses (51.9%) with omphalocele who were not artificially aborted. Intrauterine growth restriction (IUGR) was identified in four of 11 fetuses (36.4%) with gastroschisis and in 13 of 27 fetuses (48.1%) with omphalocele who were not aborted artificially. There was a high rate of associated structural anomalies with omphalocele (26/33). Karyotypic abnormalities were observed in eight of 29 tested fetuses with omphalocele (27.6%). The prognosis for a chromosomally normal fetus with omphalocele appeared to largely depend on the associated structural abnormalities and the gestational age at delivery. Despite the frequent presence of IUGR, the outcome of neonates with gastroschisis was good. Conclusions: The possibility of preterm delivery and IUGR should be considered during the management of both omphalocele and gastroschisis. For the management of omphaloceles, chromosomal abnormalities and respiratory insufficiency after birth must also be considered. Timely prenatal diagnosis and the subsequent identification of associated anomalies will improve patient care and will enable clinicians to provide appropriate counseling about the expected course. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association between the presence of liver herniation and perinatal course and outcome of fetal omphalocele. Methods: Cases of fetal omphalocele managed at our hospital between 1990 and 2006 were retrospectively reviewed and grouped according to the location of the liver. Results: Thirty-three fetal omphalocele cases were diagnosed. The chromosomal status of 29 of 33 fetuses was determined. The rate of chromosomal abnormalities in cases with an extracorporeal liver was significantly lower (2/18) than in the intracorporeal group (6/11) (P=0.028). In chromosomally normal cases, four with extracorporeal liver resulted in early neonatal death compared to none with intracorporeal liver. Five of the 21 chromosomally normal fetuses showed an abnormal volume of amniotic fluid. All five cases had extracorporeal liver and two of them resulted in neonatal death. Conclusions: Fetuses with an extracorporeal liver had a lower rate of chromosomal abnormalities than those in the intracorporeal liver group. However, in chromosomally normal cases, it appeared that extracorporeal livers might be associated with more life-threatening anomalies, amniotic fluid volume abnormalities, and a higher rate of mortality than in the group with an intracorporeal liver. Upon diagnosis of fetal omphalocele, a careful search for liver location should be conducted before counseling. [ABSTRACT FROM AUTHOR]

Background Increased serum uric acid has been postulated to directly promote oxidative stress. The aim of this study was to investigate whether serum uric acid level correlated with superoxide generation and oxidative stress in preeclampsia. Methods We assessed serum uric acid levels, plasma hydrogen peroxide levels, and plasma protein carbonyl levels in normal pregnant (n = 14) and preeclamptic women (n = 17). Serum uric acid and plasma hydrogen peroxide levels were determined by the uricase-peroxidase method, a combined enzymatic-colorimetric method. Plasma carbonyl levels were measured by ELISA. Results The mean serum uric acid values were significantly elevated in preeclampsia (6.6 ± 1.5 mg/dl) compared with normal pregnancy (4.0 ± 0.7 mg/dl) (P < 0.001). Plasma protein carbonyl levels were also significantly elevated in preeclampsia (7.72 ± 4.10 nmol/mg) compared with normal pregnancy (2.85 ± 3.06 nmol/mg) (P = 0.0011). In addition, the plasma hydrogen peroxide levels were significantly higher in preeclampsia (66.9 ± 10.9 μmol/l) compared with normal pregnancy (50.1 ± 5.6 μmol/l) (P < 0.001). Serum uric acid levels correlated significantly and positively with plasma hydrogen peroxide levels (r2 = 0.2965, P = 0.0027) and plasma protein carbonyl levels (r2 = 0.2011, P = 0.0129). Conclusion The increased serum uric acid levels correlated closely with plasma hydrogen peroxide levels and plasma protein carbonyl levels in preeclampsia. Therefore, the serum uric acid level serves as an indicator of the underlying oxidative stress in preeclampsia. [ABSTRACT FROM AUTHOR]

Many studies have shown that the prognosis of cystic hygroma associated with hydrops fetalis is poor. We report a rare case of fetal cystic hygroma and hydrops fetalis that spontaneously resolved with subsequent delivery at 37 weeks of a living female infant with Noonan’s syndrome. The prognostic significance of prenatal resolution of cystic hygroma and hydrops is uncertain. Serial evaluation of affected fetuses with ultrasound imaging may help clarify pathogenesis of cystic hygroma with associated hydrops, as well as mechanisms underlying spontaneous resolution. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Many studies have shown that the prognosis of cystic hygroma associated with hydrops fetalis is poor. We report a rare case of fetal cystic hygroma and hydrops fetalis that spontaneously resolved with subsequent delivery at 37 weeks of a living female infant with Noonan's syndrome. The prognostic significance of prenatal resolution of cystic hygroma and hydrops is uncertain. Serial evaluation of affected fetuses with ultrasound imaging may help clarify pathogenesis of cystic hygroma with associated hydrops, as well as mechanisms underlying spontaneous resolution. [ABSTRACT FROM AUTHOR]

Prenatal sonographic findings of lymphangiomas characteristically appear as thin-walled, multiseptate hypoechogenic masses. In our case, a retroperitoneal hypoechogenic mass was detected at 26 weeks of gestation by sonography. Serial sonographic examinations demonstrated multiple septations at 29 weeks of gestation, which in retrospect was a classical finding of retroperitoneal lymphangioma. MRI at 38 weeks of gestation revealed a multilocular mass, which was homogeneous, low on T1-weighted and high on T2-weighted images, in the left retroperitoneal cavity. These findings were compatible with the diagnosis of a lymphangioma. This case shows the change in characteristic imaging features, from a unilocular to multilocular pattern, of a lymphangioma with regard to gestational age. It is important to observe the size and extension of such tumors in order to determine the prospect for neonatal prognosis, as well as to make decisions on the delivery timing and style. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Without fibrinogen replacement, pregnancies in patients with congenital afibrinogenemia end in miscarriage between 6 and 8 weeks of gestation. Studies in animal models suggest that disturbance of the embryo's decidual attachment contributes to miscarriage in afibrinogenemia. Ectopic pregnancy in human congenital afibrinogenemia has not been previously documented. We present a case of right interstitial pregnancy in a woman with congenital afibrinogenemia, who had not received the recommended fibrinogen replacement for the first 6 weeks of pregnancy. The pregnancy followed a right salpingo-oophorectomy for ovarian hemorrhage. Therefore the embryo most likely entered the uterine cavity via the left tube only to move upstream into the lumen of the interstitial portion of the right tube. Our experience suggests that disturbance of the embryo's decidual attachment may have contributed to the development of an ectopic pregnancy. Therefore, fibrinogen replacement early in the first trimester is of utmost importance. [ABSTRACT FROM AUTHOR]

Objectives: To assess risk factors for the growth and development of small-for-gestational age (SGA) infants whose birth weight was less than the 10th percentile. Patients and methods: SGA infants who were admitted to the neonatal intensive care unit from 1995 to 1998 were enrolled in the study. Fifty-six SGA infants, having no chromosomal abnormalities, inherited diseases, TORCH infections, major anomaly and/or multiple birth, were divided into 34 asymmetrical and 22 symmetrical SGA infants by ≥ or <10th percentile head circumference (HC) at birth. The physical growth including HC, and the developmental quotient (DQ) and intelligent quotient (IQ) scores were evaluated up to 6 years of age. Results: Symmetrical SGA infants had lower levels of weight, height and HC, but not of total DQ at 3 years or IQ scores at 6 years of age than asymmetrical SGA infants. The 21 SGA infants who had a HC less than the 10th percentile at 1 year of age (non-catch-up group) showed lower total DQ (mean 96 vs. 105) and IQ (82 vs. 102) scores than 34 SGA infants who had not (catch-up group). Conclusions: These results suggested that psychomotor development of SGA infants depended on the HC at 1 year of age rather than that at birth. [ABSTRACT FROM AUTHOR]

BACKGROUND: Maternal exposure to polychlorinated biphenyls (PCBs) is associated with increased proportions of spontaneous abortion and stillbirth in animal studies. In Japan in 1968, accidental human exposure to rice oil contaminated with PCBs and other dioxin-related compounds, such as polychlorinated dibenzofurans (PCDFs), led to the development of what was later referred to as Yusho oil disease. OBJECTIVE: The aim of this study was to investigate the association of maternal PCB and dioxin exposure with adverse pregnancy outcomes in Yusho women. METHODS: In 2004, we interviewed 214 Yusho women (512 pregnancies) about their pregnancy outcomes over the past 36 years. Pregnancy outcomes included induced abortion, spontaneous abortion, preterm delivery, and pregnancy loss. RESULTS: In pregnancy years 1968-1977 (within the first 10 years after exposure), the proportions of induced abortion [odds ratio adjusted for age at delivery (ORadj) = 5.93; 95% confidence interval (CI), 2.21-15.91; two-tailed p< 0.001) and pretermdelivery(ORadj = 5.70; 95% CI, 1.17-27.79; p= 0.03) were significantly increased compared with the proportions in pregnancy years 1958-1967 (10 years before the incident). Spontaneous abortion (ORadj = 2.09; 95% CI, 0.84-5.18), and pregnancy loss (ORadj; 2.11; 95% CI, 0.92-4.87) were more frequent (OR = 2.18; 95% CI, 1.02-4.66), but these were not significant (p = 0.11 and p = 0.08, respectively) in pregnancy years 1968-1977. We found no significant increases in the proportions of these adverse pregnancy outcomes in pregnancies occurring during 1978-1987 or 1988-2003 compared with those in pregnancies before 1968. CONCLUSION: High levels of PCB/PCDF exposure had some adverse effects on pregnancy outcome in Yusho women. [ABSTRACT FROM AUTHOR]

BACKGROUND Neutrophil activation has been implicated in the pathophysiology of preeclampsia. The aim of this study was to investigate whether neutrophil-derived reactive oxygen species (ROS) modulate adhesion to endothelial cells in preeclampsia. METHODS We first assessed neutrophil superoxide production and neutrophil-endothelial cell adhesion in normal nonpregnant women (n = 8), normal pregnant women (n = 10), and preeclamptic pregnant women (n = 8). We then examined the effects of neutrophil-derived ROS on neutrophil-endothelial adhesion. The release of neutrophil superoxide was measured using cytochrome C reduction. RESULTS N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated superoxide production by neutrophils was significantly increased in women with preeclampsia when compared with the other two groups. Neutrophils from women with preeclampsia were more likely to adhere to endothelial cells, than were those from the other two groups (mean adhesion rate ± s.d. (%); 20.6 ± 2.7 in preeclampsia, 10.2 ± 1.2 in normal pregnancy, 11.0 ± 0.9 in normal nonpregnancy, P < 0.01). Superoxide dismutase (SOD), which dismutates the excess superoxide to hydrogen peroxide, did not affect neutrophil-endothelial adhesion. In contrast, catalase, which catalyzes the conversion of hydrogen peroxide to oxygen and water, inhibited neutrophil-endothelial adhesion in the preeclamptic group (8.1 ± 0.5%, P < 0.01). CONCLUSION Neutrophils from women with preeclampsia demonstrate increased CD11b expression and adhesion to endothelial cells. This is likely caused by elevations in superoxide and its derivative, hydrogen peroxide. [ABSTRACT FROM AUTHOR]

BACKGROUND Reduced uteroplacental perfusion and maternal cardiovascular dysfunction have been considered to be the main pathophysiological features of preeclampsia. In order to determine whether inhibition of nitric oxide synthetase (NOS) during the initial stage of placentation is associated with impaired placental development and maternal cardiovascular dysfunction, we studied the effect of N-nitro-arginine methyl ester (L-NAME), a NOS inhibitor, on morphological changes in the placenta, maternal blood pressure, and serum tumor necrosis factor-α (TNF-α) in pregnant rats during the initial stage of placentation. METHODS Pregnant Wister rats were treated during mid-gestation (days 8-14) with either L-NAME or saline. On day 20 of pregnancy the rats were killed, and maternal blood and placentas were extracted and examined. RESULTS In comparison with pregnant saline-treated control rats (blood pressure 119 ± 9 mm Hg), pregnant rats treated with L-NAME displayed significant hypertension (blood pressure 178 ± 7 mm Hg), which continued even after the withdrawal of L-NAME administration (P < 0.01). In L-NAME-treated pregnant rats, morphological examination showed decreased populations of placental trophoblast lineages, and a significant increase in placental trophoblast apoptosis. Serum TNF-a levels at day 20 of pregnancy were significantly higher in treated pregnant rats (21.2 ± 9.6 pg/ml) than in control pregnant rats (3.3 ± 2.8 pg/ml) (P < 0.01). CONCLUSIONS Inhibition of NOS at mid-gestation in pregnant rats is associated with increases in arterial pressure, placental apoptosis, and serum TNF-α, all of which have been implicated as being pathophysiological features of preeclampsia. [ABSTRACT FROM AUTHOR]

The article describes two cases of preeclamptic-eclamptic patients with clinical and neuroradiological features of posterior reversible encephalopathy syndrome (PRES), which is rare complication of preeclampsia-eclampsia. In both patients, magnetic resonance angiography (MRA) showed reversible vasospasm of large- and medium-sized cerebral arteries. The vasospasm was not present initially and was preceded by the development of vasogenic edema.

We present a case of a pregnant woman with hereditary antithrombin III deficiency and deep vein thrombosis of the left lower extremity managed by perinatal unfractionated heparin injection with antithrombin III replacement as well as by intrapartum placement of a temporary inferior vena cava filter. A massive thrombus of the right common iliac vein occurred during the intrapartum period despite antithrombin III replacement. An inserted filter could prevent fatal pulmonary embolism in this patient. Hereditary antithrombin III deficiency increases risk of thrombosis during pregnancy. However, discussion on intrapartum management, when anticoagulants are contraindicated due to possible hemorrhage, is minimal. Our experience suggests that thrombosis can occur and develop during the intrapartum period in an antithrombin III deficient woman despite antithrombin III replacement. It may be advisable to manage deliveries with temporary inferior vena cava filters to prevent fatal pulmonary embolism. [ABSTRACT FROM AUTHOR]

Aims: To review the course of monochorionic (MC) twin gestations in which one or both fetuses were diagnosed with congenital heart disease (CHD) and to identify clinical characteristics regarding the related intrauterine environmental factors particularly associated with non-twin-twin transfusion syndrome (TTTS). Methods: This study is a review of a two-center experience of MC twin pregnancies with CHD born between 2000 and 2006. Results: There were 87 MC twin pregnancies of which 11 were associated with fetal heart disease. We found concordance of CHD in 2 of the 11 twin sets. Among all of the discordant cases, the size of the affected twin was smaller. TTTS was observed in one case associated with CHD; in this case the donor twin had a coarctation of the aorta. Abnormal cord insertion was observed in 9 (69%) out of the 13 affected infants, and a significant relation was found between the presence of CHD and abnormal cord insertion. Conclusions: Of the MC twins, the smaller seemed more likely to be affected by primary structural cardiac anomalies. CHD in MC twins is possibly related to an abnormal cord insertion. Further studies are warranted to determine whether a causal relationship exists. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate whether inflammatory markers are associated with the occurrence of periventricular leukomalacia (PVL). Superoxide (O2-) production of neutrophils and plasma antioxidative superoxide dismutase (SOD) activity in umbilical cord blood were studied. Participants were preterm infants with early PVL ( n=6; three males, three females; mean birthweight 1458g [SD 517], range 620–2040g; mean gestational age 29.8wks [SD 2.9], range 27–34wks); and preterm control infants without PVL ( n=10; five males, five females; mean birthweight 1838g [SD 664], range 925–2748g; mean gestational age 30.6wks [SD 3.1], range 26–34wks). In addition, pro-inflammatory cytokine levels were measured in the umbilical cord blood. N-formyl-methionyl-leucyl-phenylalanine-induced O2- production by neutrophils in infants with early PVL was significantly higher than that in the control group. In contrast, there was no significant difference in concentrations of copper/zinc-SOD and SOD activity between groups. Concentrations of interleukin (IL)-1β and tumour necrosis factor-α (but not IL-6, IL-8, or granulocyte-colony stimulating factor) were significantly higher in infants with early PVL than in control infants. The excess O2- produced by activated neutrophils with increased pro-inflammatory cytokine production could play a role in the molecular cascade leading to white matter damage in PVL. [ABSTRACT FROM AUTHOR]

Objectives To determine relevant prenatal findings of transient abnormal myelopoiesis (TAM) that have important prognostic implications. Methods The prenatal and postnatal medical records of all cases with confirmed TAM associated with Down syndrome were reviewed retrospectively, with emphasis on prenatal sonographic findings, fetal blood analysis, neonatal outcomes, and causes of death. Results From January 1992 to December 2005, seven cases were confirmed postnatally as having TAM associated with Down syndrome. Sonography demonstrated hydrops with hepatomegaly in four, and isolated hepatomegaly in two of these seven cases. There were no findings suggestive of cardiac failure in cases of hydrops. Fetal blood analysis revealed elevated liver enzyme levels in six cases and hypoalbuminemia in four cases. Comparison of sonographic findings with fetal blood findings demonstrated an association between hydrops and hypoalbuminemia. Four of the seven cases were fatal. All fatal cases were associated with hydrops and the main cause of death was coagulopathy due to liver failure, which may have resulted from infiltration of the liver by blast cells. Conclusions Fetal TAM is associated with hepatomegaly and elevated liver enzyme levels. The prenatal finding with prognostic implications is hydrops, which may result from hypoalbuminemia due to liver failure. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess chronological changes of pulmonary blood flow in response to ambient temperature load in normal full-term neonates. Methods: Group I (n=8) neonates were maintained at 25–26°C for the first 24 h after birth, with Group II (n=7) at 32–33°C. Left pulmonary artery flow volume (Vp) and ductus arteriosus diameter were measured at 2, 4, 6, 12, and 24 h using Doppler ultrasound. Core and peripheral temperatures, as a marker for cold stress, were also evaluated over the same time frame. Results: For Group I, Vp was steady for the first 6 h after birth before gradually decreasing. In contrast, Vp for Group II significantly decreased from 2–6 h, without later changes. At 6 h after birth in Group II, mean values of both Vp and ductus arteriosus diameter were significantly lower, whereas mean value of peripheral temperature was significantly higher than values in Group I (P<0.05). Conclusion: Pulmonary blood flow in neonates placed at neutral ambient temperature stabilizes earlier than that of neonates placed at room temperatures. Changes of peripheral flow in response to ambient temperature load may be associated with decreased pulmonary blood flow through a left-to-right ductal shunt. [ABSTRACT FROM AUTHOR]

We report a case of preeclampsia associated with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome and concomitant nonbiliary acute pancreatitis and cholecystitis in the first postpartum day. A thorough investigation ruled out known etiologies of both pancreatitis and cholecystitis. Following conservative treatment, the patient's HELLP syndrome, pancreatitis, and cholecystitis resolved on the third postpartum day. Preeclampsia is associated with microvascular abnormalities that may involve the splanchnic circulation. These abnormalities may cause not only HELLP syndrome but also pancreatitis and cholecystitis. Recognizing that ischemia can damage not only the liver but also the pancreas and gallbladder, could result in improvements in the diagnosis and management of pancreatitis in patients with preeclampsia. [ABSTRACT FROM AUTHOR]

We report two cases of a complete hydatidiform mole coexistent with a live fetus diagnosed by DNA polymorphism analysis. A 27-year-old woman revealed symptoms of pre-eclampsia and ultrasound showed multicystic tumor and placenta coexistent with a live fetus at 16 weeks’ gestation. The placenta with partly hydropic change and the fetus without anomaly were consequently evacuated. Another 30-year-old woman had a multicystic mass attached to a normal placenta with a 20-week live fetus on ultrasound examination. A hysterotomy was carried out because of persistent bleeding due to placenta previa. In both cases, DNA was extracted from the placental tissue and the tumor, as well as from maternal and paternal blood. Genetic analysis demonstrated that the placental tumor consisted of only paternal origin, which is consistent with the diagnosis of complete hydatidiform mole. [ABSTRACT FROM AUTHOR]

Subependymal germinal matrix with intraventricular hemorrhage (GMIVH) is a common complication associated with delivery in preterm neonates but has rarely been observed in the fetus. Clinical and neuroradiological findings of 5 patients who were diagnosed as having fetal GMIVH with prenatal ultrasonographic examinations (US) and MRI, and postnatal MRI were reviewed retrospectively. During a seemingly uneventful pregnancy, fetal GMIVH occurred at approximately 30–33 weeks of gestation, with the absence of any known factor predisposing to fetal hemorrhage. Routine obstetric US revealed an intraventricular lesion in the enlarged ventricles. Prenatal MRI clearly demonstrated parenchymal change such as intracerebral hematoma adjacent to the subependymal and intraventricular hematoma, and periventricular leukomalacia as well as GMIVH. Although patients without parenchymal destruction (hemosiderin deposit alone) had a favorable neurodevelopmental outcome, encephalomalacia and periventricular leukomalacia contributed to long-term neurodevelopmental deficits. Evaluating parenchymal damage with prenatal MRI can therefore help to predict neurodevelopmental prognosis of the fetus with GMIVH. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Problem Oxygen radical formation by neutrophils during pregnancy is not well studied. Method of study We studied neutrophil-derived superoxide anion (O ) and nitric oxide (NO) values in 75 normal pregnant women, 12 postpartum women, and 10 non-pregnant women. O production was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c. NO production was measured by accumulation of the stable end product nitrite using a modified Griess reaction method. Results O production of neutrophils stimulated by chemotactic peptide was significantly enhanced in the early second trimester of pregnancy.l-arginine analogue-inhibitable nitrite production was induced in neutrophils from pregnant women, but not from postpartum and non-pregnant subjects. In third-trimester subjects but not non-pregnant subjects, neutrophils pre-treated withl-arginine analogues enhanced O production compared with untreated neutrophils. Conclusion These findings indicate that O and NO production by neutrophils during pregnancy were modulated separately, whereas neutrophil-derived NO might function as a regulator of O . [ABSTRACT FROM AUTHOR]

To investigate whether vascular reactivity of the umbilical artery influences differences in Doppler waveform depending on the sampling site along the cord, we studied a regional difference of endothelium-dependent vascular contractility in human umbilical artery using mechanical responses to the quick stretch of vascular smooth muscle strips. The umbilical artery resistance index (RI) values for the fetal end were significantly higher than those for the placental end. In endothelium-intact strips, stretch-induced contraction of the umbilical artery appears to decrease from the fetal to the placental end of the umbilical artery. No significant differences were noted between strips from the two locations when endothelial cells were rubbed, indicating that this regional difference is related to endothelial cell function. Indomethacin decreased the stretch-induced contraction of endothelium-intact strips, but tetrodotoxin did not affect this association, suggesting that arachidonic acid metabolism via the cyclooxygenase pathway contributes to modulation of human umbilical artery responsiveness to stretch. These findings suggest that the difference in Doppler waveform of the umbilical artery depending on the sampling site is related to differences in vascular resistance that result from endothelium-related function. [ABSTRACT FROM AUTHOR]

Purpose. P-Glycoprotein (Pgp) plays an important role in drug disposition and excretion in various tissues such as the brain, intestine, and kidney. Moreover, we have demonstrated that Pgp is expressed on the brush-border membranes of trophoblast cells in the placenta and restricts drug transfer from the maternal circulation to the fetus. However, the transport kinetics of physiologically expressed Pgp has scarcely been investigated. Methods. In this study, we assessed the functional kinetics of transport mediated by Pgp that is physiologically expressed in normal tissue by using human placental brush-border membrane vesicles (BBMVs). Digoxin and vinblastine were used as typical substrates of Pgp. Results. The uptakes of [³H]digoxin and [³H]vinblastine into BBMVs were significantly increased in the presence of an ATP-regenerating system. The ATP-dependent uptakes of [³H]digoxin and [³H]vinblastine into BBMVs exhibited saturable kinetics. The Michaelis constants (K[sub t] values) were 2.65 ± 1.80 µM and 21.9 ± 3.37 µM, respectively. In the presence of a Pgp inhibitor such as verapamil, cyclosporine A, or progesterone, the ATP-dependent uptakes of [³H]digoxin and [³H]vinblastine into BBMVs were significantly reduced. Anti-Pgp monoclonal antibody C219 completely inhibited the uptake of [³H]digoxin. Conclusions. The transport kinetics of [³H]digoxin and [³H]vinblastine by physiologically expressed Pgp were successfully evaluated by using BBMVs prepared from normal human placenta. The present method enabled us to evaluate the function of physiologically expressed Pgp and is superior to the use of cultured transfectants in terms of the yield of vesicles. The present method may also be applicable to investigating the influence of various factors such as the genotype of the MDR1 gene or various pathophysiologic states of neonates on the function of Pgp. [ABSTRACT FROM AUTHOR]