Three-dimensional ultrasound findings in cornelia de lange syndrome: a case report.

Introduction. The objective is to report a case of Cornelia de Lange syndrome (CdLS) diagnosed by detailed observations using three-dimensional sonography. Case Report. A 33-year-old healthy multipara was referred to our hospital at 34-week gestation after severe fetal growth restriction, congenital heart anomaly, and antebrachium abnormality were diagnosed during the third trimester. Further sonography diagnosis on cardiac abnormalities diagnosed the existence of ventricular septal defect in the outflow tract, atrioventricularis communis, and truncus arteriosus communis where the pulmonary artery branched from the common arterial trunk. As for abnormalities of the forearms, ectrodactylia and monodactylism were suspected and the abnormalities were observed sterically by using three-dimensional sonography. A 1986 g (1.07 percentile) male newborn was delivered by assisted breech extraction at 37-week gestation. After birth, from characteristic facies including bushy eyebrow, broad nasal bridge, micrognathia, and abnormalities of the forearms (ectrodactylia and monodactylism), the case was diagnosed with CdLS. Conclusion. Through detailed observation including abnormalities of fingers, we could exemplify this very rare disease as an antenatal diagnoses for fetal growth retardation.

The correlation of maternal uric acid concentration with small-for-gestational-age fetuses in normotensive pregnant women.

AIM: Elevated maternal serum uric acid is associated with small-for-gestational-age (SGA) fetuses. We investigated whether uric acid concentrations in normotensive pregnant women are correlated with fetal growth and related to kidney function. METHODS: We carried out a case-control study using 40 patients who delivered SGA fetuses identified from the perinatal database and 80 patients who delivered appropriate-for-gestational-age (AGA) fetuses as the controls at Okayama University Hospital. Blood pressure, serum uric acid and creatinine level were measured in the patients' third trimester. RESULTS: Maternal serum uric acid (p = 0.0003) and creatinine (p < 0.0001) concentrations, as well as systolic and diastolic blood pressures (p =0.014 and 0.037, respectively), were significantly increased in the SGA group. There was a strong negative correlation between serum uric acid levels and birth weights (r = -0.59; p = 0.006) and a significant positive correlation between maternal serum uric acid and creatinine levels (r = 0.43; p < 0.05) in cases of severe SGA (<5th percentile). Multiple linear regression analysis indicated that uric acid is an independent risk factor for SGA. CONCLUSIONS: Increasing maternal uric acid concentrations were associated with slightly impaired kidney function and SGA in normotensive pregnant women.

Effects of intermittent high glucose on BeWo choriocarcinoma cells in culture.

AIM: The aim of this study was to investigate the cellular effects of intermittent high glucose on the human BeWo placental choriocarcinoma cell line, used as a model of the effects of glucose fluctuation in diabetic pregnancies. MATERIALS AND METHODS: BeWo cells were subjected to three different glucose conditions for 48 h: 7 mmol/L (control), 42 mmol/L (high glucose), or 7 and 42 mmol/L glucose (intermittent, alternated every 6 h). Cell viability was assessed using cell counts, a cell proliferation assay, and a cell viability assay. Apoptosis was also studied using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and by immunocytochemistry of fractin, the N-terminal fragment of actin, which can distinguish apoptotic from necrotic cells. Furthermore, the expression of the well-known survival factors of trophoblast cells, heparin-binding epidermal growth factor-like growth factor and leptin, was evaluated by real-time polymerase chain reaction and Western blot analyses. RESULTS: Intermittent high-glucose conditions significantly decreased cell viability and enhanced apoptosis compared with control or continuous high-glucose conditions. Furthermore, the expression of heparin-binding epidermal growth factor-like growth factor, but not that of leptin, was significantly increased under intermittent high-glucose conditions compared to its expression under either control or continuous high-glucose conditions. CONCLUSIONS: These data indicate that intermittent high glucose is more deleterious to BeWo cells than continuous high-glucose conditions. Although further in vitro and in vivo study is necessary, excess fluctuation of glucose levels in the placental circulation might be involved in the impairment of placental development leading to the placental dysfunction.

Expression of antiangiogenic prolactin fragments in the placentas of women with pregnancy induced hypertension.

It has been reported that prolactin (PRL) is cleaved to 14 or 16 kDa fragments by cathepsin D in vitro and in vivo, and that such fragments exhibit antiangiogenic and proapoptotic properties. The aim of this study was to investigate the relationship between pregnancy induced hypertension (PIH) and the placental expression of antiangiogenic PRL fragments and cathepsin D. Placental expression of PRL fragments and cathepsin D was evaluated by Western blot analysis in a group of 9 pregnant women consisting of 5 normal pregnancies and 4 severe PIH cases. Antiangiogenic PRL fragments were detected in 4 placental samples from all PIH cases but not detected in those from normal pregnancies (p<0.05). The expression of cathepsin D in PIH placentas was significantly lower than that in those without PIH (p<0.05), while the placental expression of procathepsin D was significantly greater in PIH cases than in the normal pregnancies (p<0.05). These data suggest that antiangiogenic PRL fragments in the placenta may be present only in PIH cases, and that PRL fragments in the placenta might be implicated in the pathophysiology of PIH.

Circulating levels of ciliary neurotrophic factor in normal pregnancy and preeclampsia.

Ciliary neurotrophic factor (CNTF) has been shown to decrease food intake in mouse models of obesity and to improve insulin sensitivity. It is well known that tight regulation of glucose metabolism is essential for successful gestational outcomes (e.g. fetal growth), and that abnormal insulin resistance is associated with preeclampsia (PE). To investigate the possibility that CNTF might be involved in the regulation of insulin resistance during pregnancy, circulating levels of CNTF were assessed in non-pregnant, normal pregnant, postpartum, and pregnant women with PE. Sera from healthy non-pregnant women (n = 10), pregnant women (n = 30:1st trimester; n = 10, 2nd trimester n = 10; 3rd trimester; n = 10), postpartum women (n = 10), and patients with PE (n = 11) were studied with Western blotting. Circulating CNTF was detected by Western blotting, and the levels of CNTF in pregnant women were decreased as compared with those in non-pregnant women, and tended to decrease as pregnancy progressed. A significant decrease was found in PE as compared with normal pregnancy. Circulating CNTF might be associated with physiological and abnormal insulin resistance during pregnancy.

Elevated level of serum retinol-binding protein 4 in pregnancy-induced hypertension.

AIM: Recent progress in adiposcience has revealed several important adipose-tissue-originated factors, so-called adipokines. Retinol-binding protein 4 (RBP4), a protein expressed and secreted by adipocytes, has been identified as a novel regulator of insulin resistance. Physiological insulin resistance occurs during the pregnancy of mammals to accommodate fetal growth, and it has been suggested that insulin resistance and hyperinsulinemia might also be associated with pregnancy-induced hypertension (PIH). In order to shed light on the role of RBP4 during pregnancy, we attempted to assess RBP4 levels during pregnancy. Fetal growth could be affected by aberrant regulation of RBP4 levels in fetal circulation per se, so we examined the RBP4 levels in cord blood samples of growth restricted cases. METHODS: Circulating RBP4 levels were examined in non-pregnant and pregnant healthy women using Western blotting. Also, RBP4 levels in normal pregnancy and PIH were quantitated using Dot-blot analysis. RBP4 levels in cord blood samples also were evaluated in selected cases. RESULTS: RBP4 levels tended to decrease after early gestation with no obvious difference between mid- to late-gestation. RBP4 levels were increased in pregnant women with PIH compared with normal pregnancies (P < 0.01). RBP4 levels were decreased in the cord blood of PIH pregnancies and light-for-dates infants without obvious causes for intrauterine growth restriction compared with normal pregnancies (P < 0.01). CONCLUSIONS: These results suggest that circulating RBP4 could be elevated in PIH, where maternal glucose metabolism is perturbed, and that RBP4 levels in cord blood might be closely associated with fetal growth.

Thrombocytopenia in preterm infants with intrauterine growth restriction.

Sick preterm infants often have thrombocytopenia at birth, and this is often associated with intrauterine growth restriction (IUGR), or birth weights less than the 10th percentile. The pathogenesis of the thrombocytopenia and its importance in IUGR are still unclear. We studied the characteristics of preterm IUGR infants with thrombocytopenia. Twenty-seven singleton Japanese preterm IUGR infants were born between January 2002 and June 2007 at Okayama University Hospital. Infants with malformation, chromosomal abnormalities, alloimmune thrombocytopenia, sepsis, and maternal aspirin ingestion were excluded. The infants were divided into group A (n=8), which had thrombocytopenia within 72 h after birth, and group B (n=19), which did not. There were significant differences in birth weight, head circumference, umbilical artery (UA)-pulsatility index (PI), middle cerebral artery-PI, UA-pH, UA-pO2, and UA-pCO2. The infants in group A were smaller, had abnormal blood flow patterns, and were hypoxic at birth. We speculate that the infants with thrombocytopenia were more severely growth-restricted by chronic hypoxia. Thrombocytopenia is an important parameter for chronic hypoxia in the uterine.

Relation between neonatal jaundice and oncostatin M, hepatocyte growth factor and soluble gp130 levels in umbilical cord.

OBJECTIVES: Oncostatin M (OSM), hepatocyte growth factor (HGF) and soluble glycoprotein 130 (sgp130) have been demonstrated to be involved in fetal liver development. In this study, we examined the relation between neonatal jaundice and OSM, gp130 or HGF levels in umbilical cord blood. DESIGN: A cross-sectional study of 160 neonates born at Okayama University Hospital. SETTING: Tertiary referral center serving a population of three million. METHODS: The serum concentrations of OSM, HGF and sgp130 in umbilical venous cord blood were measured and compared with the clinical records of these neonates. RESULTS: The HGF level was correlated to both gestational week (p=0.007) and birthweight (p=0.015), as well as to total bilirubin on Day 1 (p=0.032). In preterm neonates, the HGF levels were lower in neonates who received phototherapy (photo group) than in those who did not receive phototherapy (non-photo group) (p=0.002). In contrast, in term neonates, OSM levels were lower in the photo group than in the non-photo group (p=0.0003). CONCLUSIONS: These findings suggest that the phototherapy requirement for neonatal jaundice may be associated with lower umbilical HGF concentration in preterm neonates and with lower umbilical OSM concentration in term neonates.