脐血流异常对选择性宫内生长受限代谢组学影响的初步探讨

目的:探讨合并脐血流异常对选择性宫内生长受限(s IUGR)脐血血浆代谢组学的影响。方法:纳入6对合并脐血流异常及3对脐血流正常(对照组)的s IUGR双胎,利用气相色谱-飞行时间质谱技术(GC-TOF/MS)对双胎脐血进行代谢物检测,通过主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)对质谱数据进行多元变量模式识别分析,根据模型的变量投影重要性、学生t检验筛选可能的标记物,并进行代谢通路分析。结果:合并脐血流异常s IUGR筛选出17种有统计学意义的差异代谢物。其中谷氨酸、草酸、环亮氨酸、N-(2-羟乙基)亚氨基二乙酸及L-犬尿氨酸在s IUGR合并脐血流异常组增加,天冬氨酸、N-乙酰-L-天冬氨酸、乳酸、L-苏糖、酪氨酸、甘氨酸、富马酸、β-甘露糖基甘油酸、β-丙氨酸、亚油酸、棕榈酸和马来酰胺酸则降低。结论:GC-TOF/MS方法证实合并脐血流异常的s IUGR代谢组学发生改变,主要体现在脂质、碳水化合物、氨基酸、能量、核酸、辅助因子和维生素代谢等方面。     

脐动脉波形异常伴胎儿宫内生长迟缓患者胎盘血管内皮生？…

目的 探讨胎儿脐动脉波形异常伴宫内生长迟缓（ＩＵＧＲ）与胎盘血管内皮生长因子（ＶＥＧＦ）表达水平的关系,并得出胎盘的氧水平。方法 应用彩色多谱勒超声,对４０例妊娠晚期妇女进行胎儿脐动脉搏动指数（ＰＩ）、阻力指数（ＲＩ）及收缩期末最大血流速度与舒张期末最小血流速度比值（Ｓ／Ｄ）测定,根据脐动脉波形变化分为４个组。脐动脉波形异常伴ＩＵＧＲ组（ＡＶＡＷ组）、脐动脉波形异常不伴ＩＵＧＲ组（ＡＶＮＷ组）、脐     

Spontaneous intrauterine umbilical artery thrombosis leading to severe fetal growth restriction

Intrauterine thrombosis of umbilical cord vessels is a rare event (2.5-4.5/10,000) and usually followed by poor fetal outcome. We present the rare case of spontaneous intrauterine thrombosis of an umbilical artery leading to severe intrauterine growth restriction (IUGR) and provide clinical and pathological findings. A 28-year-old nulliparous third gravida was referred to our institution because of IUGR at 32+4 weeks of gestation. Fetal growth had been appropriate until the 31st week of gestation and had stopped thereafter. There were no signs of abruption of the placenta and no structural abnormalities except an absent paravesical colour Doppler flow in the region of the right umbilical artery. Other Doppler measurements, karyotype and TORCH serology were normal. Intermittent non-reassuring fetal heart rate led to cesarean section at 34+3 weeks of gestation. A healthy girl with measurements on the 3rd centile was born (weight of 1,590 g, length of 41 cm and head circumference of 29 cm). Gross examination displayed an elongated, highly twisted umbilical cord with a length of 70 cm, central insertion and three umbilical vessels. Microscopic examination confirmed the diagnosis of umbilical artery thrombosis along the entire length of the umbilical cord. Calcification within the thrombus and microcalcification in occluded chorionic vessels were observed as well as hemorrhagic endovasculitis and endangiopathia obliterans in the stem villi arteries. This fetal thrombotic vasculopathy (FTV) comprised about 40% of the parenchyma. The coagulation parameters and blood counts of the mother and the infant were normal apart from transient neonatal thrombocytopenia. The reason for thrombosis remained unclear but could be attributed to the elongated and highly twisted umbilical cord. Intrauterine arterial thrombosis may cause severe IUGR. This condition might be detectable by ultrasound in the course of an IUGR workup, especially when no other reasons can be found.     

Decreased vascularization and cell proliferation in placentas of intrauterine growth-restricted fetuses with abnormal umbilical artery flow velocity waveforms

OBJECTIVE: The purpose of this study was to compare the morphologic features of placentas in severe intrauterine fetal growth restriction with abnormal umbilical artery blood flow velocity waveforms and normal gestation. STUDY DESIGN: Immunohistochemical methods were used to evaluate cell proliferation, vascular density, and alpha-smooth muscle actin expression by stromal cells in a group of 9 age-matched intrauterine growth-restricted and control placentas at 25 to 41 weeks of gestation. RESULTS: Fewer MIB1-positive nuclei were observed in both trophoblast and stromal cell populations in intrauterine growth restriction, which indicates fewer cells in cycle. Furthermore, a greatly reduced vascular density was observed, along with higher levels of alpha-smooth muscle actin expression in stromal cells. CONCLUSION: Intrauterine growth-restricted placentas show reduced cell proliferation in both trophoblast and stromal cell compartments. Peripheral villous vascularization is highly reduced.     

Single umbilical artery is associated with an increased incidence of structural and chromosomal anomalies and growth restriction

The objective to characterize neonatal outcome associated with ultrasonographic identification of a single umbilical artery. Pregnancies diagnosed with single umbilical artery antenatally were identified. All prenatal/antenatal and pediatric records were reviewed for maternal demographics, associated anomalies, karyotypic analysis, pregnancy complications, and neonatal outcome. Twenty-seven pregnancies complicated by fetal single umbilical artery were identified. Of the 27 pregnancies, 5 (18.5%) underwent pregnancy termination and 1 (3.7%) experienced fetal demise. Of the 21 liveborn infants, 4 (19%) died within the first year of life. Sixty-seven percent of fetuses had an associated structural anomaly. Sixteen of the 27 pregnancies underwent amniocentesis and 7 of these were chromosomally abnormal. All of the karyotypically abnormal fetuses had a structural defect in addition to the single umbilical artery. Of the six fetuses without any associated structural or chromosomal anomalies, three (50%) demonstrated growth restriction. Single umbilical artery is relatively rare finding. When a single umbilical artery is identified, a vigilant search for associated anomalies should be undertaken. Pregnancies identified as having fetuses with associated structural anomalies should be offered amniocentesis. Pregnancies with isolated single umbilical artery should be carefully monitored for evidence of fetal growth restriction.     

The effect of maternal exercise on umbilical artery velocimetry waveforms in intrauterine growth retardation.

Eighteen pregnant women affected with fetal growth retardation in the last trimester were exercised. The mean maternal heart rate increased significantly from 140 beats per minute (bpm) (120-188 bpm) at rest to 172 bpm (163- 178 bpm) after exercise. The mean exercise intensity was 65% (56-85%) of submaximal exercise. Maternal systolic blood pressure rose significantly from a mean of 116 mmHg (100-140 mmHg) to 159 mmHg (120-190 mmHg) and the diastolic blood pressure rose significantly from a mean of 72 mmHg (55-110 mmHg) to 90 mmHg (80-110 mmHg). The umbilical artery pulsatility index (PI), after an initial decrease, showed a 12% rise at 8, 16 and 30 minutes of recovery. Patients who smoked had a significantly higher umbilical artery PI before and after exercise. Less active Patients had a higher PI before and after exercise than active ones. Infants weighing 1.9-2.5 kg at birth had a higher PI than those weighing 2.6-3.3 kg. Male fetuses had a significantly higher PI than female fetuses.     

Umbilical artery velocity waveforms and intrauterine growth retardation

A continuous-wave Doppler unit was used to obtain umbilical artery velocity waveforms and to calculate the peak-systolic/diastolic ratio, a reflection of vascular resistance distal to the point of measurement. A total of 587 examinations were performed on 189 women between 18 to 42 weeks' gestation. The neoriates were divided in four groups based on their centile birth weight: <25%, 25% to 50%, 51% to 75%, and >75% for that gestational age. In all four groups the placental vascular resistance as reflected by the systolic/diastolic ratio fell progressively from the 24 weeks onward. In the lower weight group, placental vascular resistance between 31 to 39 weeks' gestation was higher than in the other three groups (p < 0.05). For measurements taken between 31 and 39 weeks' gestation we calculated the predictive value of this test in identifying the small-for-gestational age fetus. A ratio of ≥3 was defined as abnormal. For the entire population tested, sensitivity was 78% and the specificity was 83%. The predictive value of a positive test was 49%, but when hypertension was present, it was 66%. These findings may prove useful in identifying and managing pregnancies at risk for intrauterine growth retardation.     

胎儿宫内生长迟缓患者脐动脉波形异常与胎盘病理改变的关系

目的　探讨胎儿宫内生长迟缓（IUGR）患者胎儿脐动脉波形异常与胎盘重量、体积及各级绒毛血管数量的关系。方法　选择分娩前1周内,患IUGR或B超检查有胎儿脐动脉波形异常的患者40例,分为脐动脉波形异常伴IUGR10例为研究组;脐动脉波形异常不伴IUGR（AN）;脐动脉波形正常伴IUGR（NA）,脐动脉波形正常不伴IUGR（NN）各10例为对照组。用免疫组织化学SP法,检测以上各组胎盘干血管中α-平滑肌肌动蛋白（α-smoothmuscleactin,α-SMA）表达,以确定各级绒毛和各级血管,比较研究组和各对照组间胎盘重量、体积大小、各级绒毛及血管数量。结果　（1）研究组胎盘重量、体积分别为（283.40±23.82)g及（234.60±52.08)cm     

Validity of umbilical artery Doppler waveform versus umbilical vein Doppler waveform in the prediction of neonatal outcome in intrauterine growth restriction cases

ObjectiveTo assess the neonatal outcome in relation to umbilical vein Doppler compared to umbilical artery Doppler in growth restricted fetuses.MethodsA total of 72 pregnant women with singleton pregnancy between 28 and 38 weeks of gestation with risk of developing intrauterine growth restriction (IUGR) were recruited to the study. All women were subjected to full assessment via detailed history, clinical examination, obstetric assessment, routine laboratory assessment and ultrasonography examination for fetal assessment. Doppler examination of umbilical artery (UA) and umbilical vein (UV) was performed. Absent or reversed UA end diastolic flow (EDF) and pulsatile flow in the umbilical vein were examined for their efficacy to predict critical outcomes (still birth, neonatal death, IUGR).ResultsA total of 13 deaths (18%) were reported; 13.9% were neonatal deaths and 4.2% were stillbirths. Fetuses were grouped according to Doppler parameters: those with normal Doppler finding (n = 35), those with resistance index (RI) (n = 20), those with Absent UA EDF (n = 10) and those with reversed UA EDF (n = 7). Pulsatile UV waveform was reported among 9.7% of patients all of them had reversed UA EDF. Patients with absent/reversed EDF have significant association with critical neonatal outcomes as lower birth weight, perinatal deaths, and lower Apgar score. UV Doppler was abnormal in patients with more severe deterioration (patients with reversed UA EDF) while it was normal in all patients with increased RI and absent UA EDF. All cases with Pulsatile UV Doppler have shown higher incidence of critical neonatal outcomes.ConclusionUV Doppler assessment can aid in detection and prediction of critical perinatal outcomes however, it required further evaluation and assessment.     

Free fetal DNA is not increased before 20 weeks in intrauterine growth restriction or pre-eclampsia

BACKGROUND: The aim of this study was to quantify maternal plasma fetal DNA and total DNA in early pregnancy in intrauterine growth restriction (IUGR) or pre-eclampsia (PET). METHODS: A nested case control study was carried out in a University Teaching Hospital. Plasma samples were obtained from 1993 women before 20 weeks of gestation. Pregnancies complicated by IUGR or PET were identified and compared to controls. DNA was extracted and real-time quantitative PCR applied for the SRY and beta-actin genes. IUGR or PET groups were compared to controls using the chi(2) and Wilcoxon rank sum tests. RESULTS: SRY was detected in 86% of IUGR (31/36), 94% of PET (15/16) and 78% of controls (56/72). The median SRY was similar in women with IUGR (28 GE/mL) or PET (30.5 GE/mL) and controls (27.5 GE/mL). beta-actin was increased in the IUGR group (3975 GE/mL) compared to controls (1835 GE/mL) (p = 0.045). Cigarette consumption was greater in the IUGR group compared to controls (p = 0.004). CONCLUSIONS: Fetal DNA quantitation in maternal plasma before 20 weeks is not a useful predictor of IUGR or PET. beta-actin levels were elevated before 20 weeks in women with IUGR and may be a marker of maternal susceptibility to this condition.     

Stereological quantification of placental villus vascularization and its relation to umbilical artery Doppler flow in intrauterine growth restriction

The aim of this study was to investigate the changes in the number of vessels within tertiary stem villi and intermediate/terminal villi which may be responsible for the abnormalities in placental vascular resistance and Doppler velocity index values in growth-restricted fetuses. The placentas of 20 cases with intrauterine growth restriction and 30 cases which were appropriate for gestational age were studied. The umbilical artery resistance index, pulsatility index and systolic to diastolic ratio were measured in each case. The vessels were quantified by a stereological method described previously and vascular surface density and the volume portion of the villi were calculated. The placentas of preterm and term cases with intrauterine growth restriction displayed significant reductions in the vascular surface density of stem and intermediate/terminal villi and volume portion of intermediate/terminal villi stroma when compared with gestation-matched normally grown cases (p<0.05). There was no significant correlation between Doppler index values of the umbilical artery and the stereological parameters of the intermediate/terminal and stem villi in the intrauterine growth restriction group (p>0.05). Some of the pregnancies with intrauterine growth restriction (six patients) with normal Doppler flow velocity waveforms had reduced vascularization in the placentas, and these pregnancies were found to have no perinatal complications. We conclude that,although the placental villi show reduced vascularization in pregnancies with intrauterine growth restriction, the Doppler indices may be normal and this normal flow pattern is related to reduced complication rate.     

Maternal and fetal plasma endothelin levels in intrauterine growth restriction: relation to umbilical artery Doppler flow velocimetry

The objective of this study was to examine maternal and fetal endothelin-1 (ET-1) in pregnancies complicated with intrauterine growth restriction (IUGR) and to correlate these data with umbilical artery Doppler flow velocity waveforms (FVW). Higher mean maternal (13.8 +/- 6.4 vs 9.2 +/- 3.4 pmol/L, p < 0.05) and fetal (18.5 +/- 9.6 vs 11.7 +/- 6.9 pmol/L, p < 0.05) ET-1 levels were found in pregnancies complicated with IUGR than in controls. Fetal ET-1 level was related to birth weight percentile for gestational week. Maternal and fetal ET-1 concentrations were not related to umbilical artery Doppler flow S/D ratio, PI and RI. Maternal or fetal ET-1 concentrations were also not related to umbilical artery pH, PO2 and PCO2. Pregnancy-induced hypertension was significantly associated with an elevated fetal and maternal ET-1 concentration. In conclusion, increased production and secretion of ET-1 may play a role in the pathophysiology of idiopathic IUGR. Over-production of ET-1 in IUGR is not associated with increased placental resistance as reflected in abnormal umbilical artery Doppler FVW.     

Blood pressure is elevated in normotensive pregnant women with intrauterine growth restriction

OBJECTIVE: To assess the relationship between blood pressure pattern and intrauterine growth restriction in normotensive pregnant women. STUDY DESIGN: Twenty-four-hour ambulatory blood pressure was consecutively performed between 32 and 34 weeks in 139 normotensive, non-proteinuric, primigravidae with intrauterine growth restriction (IUGR) and in 140 primigravidae, matched for age and gestation, who were and remained normotensive throughout pregnancy and whose fetuses had regular fetal growth, who served as controls. RESULTS: Although all measures were within the normotensive range, blood pressure of mothers with IUGR were significantly higher than controls. Twenty-four-hour mean, daytime, and nighttime systolic were 119.9+/-11.9, 122.6+/-11.7, 114.4+/-13.3 mmHg, in women with IUGR and 108.0+/-7.4, 109.2+/-7.3, 102.1+/-8.5 mmHg, in controls. Twenty-four-hour diastolic average, daytime, and nighttime diastolic (mean+/-S.D.) 78.1+/-9.3, 69.2+/-10.6, 67.2+/-9.0 mmHg, in women with IUGR and 64.1+/-5.7, 66.0+/-5.7, 58.2+/-6.3 mmHg, in normal pregnant women. All differences p<0.0001. CONCLUSIONS: Pregnant women with idiopathic IUGR have blood pressure higher than normal. Although within clinic normotensive range, slightly higher levels of blood pressure can alter uterine and placental perfusion and determine fetal growth restriction.     

Reduced fetal platelet counts in pregnancies with abnormal Doppler umbilical flow waveforms

Fetal and maternal platelet counts were correlated with antenatal assessment of the umbilical-placental waveform. Forty singleton pregnancies were studied using Doppler ultrasound, and placental resistance was categorized as normal or high according to the systolic/diastolic ratio. We performed platelet counts on maternal and cord blood taken at the time of cesarean section. The high-resistance group had a mean fetal platelet count (218 +/- 53 x 10(3)/microliters) significantly lower than that of the normal-resistance group (314 +/- 76 x 10(3)/microliters) (P less than .001). This difference was evident in both the hypertensive and nonhypertensive subgroups of the high-resistance group. There was no difference in mean maternal platelet counts between the high- and normal-resistance groups.     

Maternal and umbilical venous adrenomedullin and nitric oxide levels in intrauterine growth restriction

Objective.?To verify whether adrenomedullin (AM) and nitric oxide (NO) concentrations are changed in the maternal and fetal circulation in pregnancies complicated by intrauterine growth restriction (IUGR) compared to normal pregnancies, and to determine any relationship between them.

Methods.?Forty-six small for gestational age (SGA) and 34 appropriate for gestational age (AGA) infants were included in the study. Umbilical and maternal venous AM and NO concentrations were determined.

Results.?Umbilical NO concentrations in SGA infants (mean ± SD; 176.2 ± 75.8 μmol/L) were significantly greater than in AGA infants (143.4 ± 39.2 μmol/L) (p = 0.015). However, umbilical AM concentrations were similar in SGA and AGA infants with 14.2 ± 4.4 pmol/mL and 14.5 ± 6.2 pmol/mL, respectively (p > 0.05). There was no relationship between NO and AM levels in umbilical blood (r = 0.09, p = 0.40). No difference was found between either AM or NO levels in the maternal plasma of the two groups.

Conclusions.?We suggest that NO is increased in the fetoplacental circulation in SGA infants probably as a response to decreased blood flow, whereas AM is not. Additionally, increased NO in the fetoplacental circulation was found to be independent from AM secretion.