表皮生长因子及其受体与胎儿出生体重的关系

目的探讨表皮生长因子（ＥＧＦ）及其受体与胎儿出生体重的关系。方法采用酶联免疫吸附测定法对正常非孕妇女１５例（对照组）、足月正常体重儿４０例（正常体重儿组）、ＩＵＧＲ儿４０例（ＩＵＧＲ儿组）、巨大儿２５例（巨大儿组）的母血清、脐血清及羊水中ＥＧＦ浓度进行测定,同时采用免疫组化方法对以上各组胎盘及胎膜上ＥＧＦ受体（ＥＧＦＲ）进行测定。结果各组母血、脐血及羊水中ＥＧＦ浓度明显高于对照组（Ｐ＜００５）。ＩＵＧＲ儿组母血、脐血及羊水中ＥＧＦ浓度低于正常体重儿组,差异有显著性。巨大儿组母血、脐血及羊水中ＥＧＦ浓度与正常体重儿组比较,差异无显著性。在ＩＵＧＲ儿组胎盘及胎膜上ＥＧＦＲ表达明显低于正常体重儿组（Ｐ＜０．０１）,巨大儿组胎盘上ＥＧＦＲ表达高于正常体重儿组。结论ＥＧＦ及其受体与ＩＵＧＲ的发生有关,在妊娠后期测定母血及羊水中ＥＧＦ浓度,对评价胎儿的生长发育具有重要意义。     

胎儿生长迟缓孕妇淋巴细胞姐妹染色单体的互换频率

目的：了解胎儿生长迟缓（ＩＵＧＲ）孕妇外周血及新生儿脐血姐妹染色单体互换（ＳＣＥ）频率的变化。方法：应用姐妹染色单体互换技术，对１４例单纯性ＩＵＧＲ孕妇（ＩＵＧＲ组）及９０例正常孕妇（对照组）的外周血及其所分娩新生儿脐血ＳＣＥ频率进行测定。结果：ＩＵＧＲ组外周血及脐血ＳＣＥ频率分别为１０．５３±２．６９，７．２５±１．３４；对照组外周血及脐血ＳＣＥ频率分别为７．５８±０．３２，５．０５±０．２９；两组比较，差异有极显著性（Ｐ均＜０．０１）。ＩＵＧＲ组外周血及脐血ＳＣＥ频率全部异常。结论：ＩＵＧＲ与遗传物质损伤有关，ＳＣＥ频率有可能作为一项诊断ＩＵＧＲ的新指标。     

胎儿胰岛素样生长因子-Ⅰ的检测及意义

目的评估胰岛素样生长因子Ⅰ（ＩＧＦⅠ）在胎儿、胎盘生长发育中的作用。方法用放射免疫分析法（ＲＩＡ）测定大于胎龄儿（ＬＧＡ）组３０例,适于胎龄儿（ＡＧＡ）组３６例及小于胎龄儿（ＳＧＡ）组３６例的脐血清ＩＧＦⅠ的水平。用线性相关分析法分析各组变量之间的相关关系。结果３组胎儿脐血清ＩＧＦⅠ与胎龄、胎儿体重、胎盘重量均呈显著正相关（ｒ＝０．３２,Ｐ＜０．００１;ｒ＝０．６８,Ｐ＜０．００１;ｒ＝０．７５,Ｐ＜０．０１）,其中与胎盘重量呈高度正相关。脐血清ＩＧＦⅠ水平,ＡＧＡ组为１４４５９±４６．７３μｇ／Ｌ;ＳＧＡ组为９０．８０μｇ／Ｌ（ｔ＝４．７,Ｐ＜０．００１）,ＬＧＡ组为２０９１７μｇ／Ｌ（ｔ＝７．９７,Ｐ＜０．００１）。结论ＩＧＦⅠ是胎儿、胎盘生长发育的重要调节因子,对巨大儿、小于胎龄儿的形成有重要作用。     

胎儿宫内发育迟缓时胎盘病理改变与孕妇血及脐血中一氧化氮水平的关系

目的了解胎儿宫内发育迟缓（ＩＵＧＲ）时胎盘病理改变与母血及脐血中一氧化氮（ＮＯ）水平的关系。方法对１９９７年１１月～１９９８年１０月３８例妊娠合并胎儿宫内发育迟缓（ＩＵＧＲ组）及３０例正常孕妇（对照组）分娩后的胎盘及胎儿附属物进行分析。用隔还原显色法测定母血及脐血ＮＯ水平。结果ＩＵＧＲ组中２６例有胎盘、脐带病理改变（６８．４２％）。主要表现为绒毛发育迟缓及绒毛炎;对照组中５例有胎盘病理改变（１６．６７％）,两组比较差异有极显著性（Ｐ＜０．０１）;ＩＵＧＲ组中母血及脐血ＮＯ水平均低于对照组（Ｐ＜０．０５,Ｐ＜０．０１）;ＩＵＧＲ组中２６例胎盘病理改变明显,其母血及脐血ＮＯ水平低于胎盘无明显病理改变者（Ｐ＜０．０５,Ｐ＜０．０５）;两组脐血ＮＯ水平均高于母血ＮＯ水平（Ｐ＜０．０１,Ｐ＜０．０５）,两组脐血与母血ＮＯ水平均有相关性（ｒ＝０．５４７５,ｒ＝０．８５０６）;脐血ＮＯ水平与新生儿体重在ＩＵＧＲ组未发现明显相关性（ｒ＝０．２８３８）。结论ＩＵＧＲ时,胎盘发生明显病理变化,导致母血及脐血中ＮＯ的水平降低。     

PGE2与胎儿胎盘循环

目的　探讨前列腺素Ｅ２（ＰＧＥ２ ）对正常妊娠及妊高征孕妇胎儿胎盘循环的调节作用。　方法　在５０例足月正常孕妇（对照组）及３７例妊高征合并ＩＵＧＲ孕妇（妊高征组）中,利用共焦点激光扫描显微镜测定了ＰＧＥ２对人脐静脉内皮细胞（ＨＵＶＥＣ）内游离钙离子（Ｃａ２＋ ）ｉ动态变化的影响,同时用放免法测定了其脐静脉血中ＰＧＥ２浓度。　结果　ＰＧＥ２ 使两组ＨＵＶＥＣ中（Ｃａ２＋ ）ｉ上升, 脐血中ＰＧＥ２ 值在妊高征组为５．４±０．６ ｐｇ／ｍ ｌ与对照组的１５．３±１．２ ｐｇ／ｍ ｌ相比,显示有意义的低值（Ｐ＜０．０５）。　结论　ＰＧＥ２ 可能为胎儿胎盘循环的血管扩张因子;妊高征组脐血中ＰＧＥ２ 浓度降低使胎儿胎盘血流阻力增加可能影响胎儿生长发育     

胰岛素样生长因子 -Ⅰ与胎儿出生体重的关系

目的了解胰岛素样生长因子Ⅰ（ＩＧＦⅠ）在胎儿生长发育中所起的作用。方法选择１７１例产妇及其所分娩的新生儿１６４例，根据出生体重将新生儿分为大于胎龄儿（ＬＧＡ）组：产妇７７例、新生儿６４例；适于胎龄儿（ＡＧＡ）组：产妇５９例、新生儿５９例；小于胎龄儿（ＳＧＡ）组：产妇３５例、新生儿４３例。用放射免疫法测定血清中ＩＧＦⅠ的浓度。结果母血中ＩＧＦⅠ浓度均高于脐血，两者间存在浓度梯度（Ｐ＜０．０１）；母、脐血中ＩＧＦⅠ浓度随孕周增加，至３９～４０周达顶峰；３３～４０周间除ＳＧＡ组外，血中ＩＧＦⅠ浓度与新生儿出生体重呈正相关（ｒ＝０．９１～０．９８）；ＳＧＡ组母、脐血ＩＧＦⅠ浓度与ＡＧＡ组相比，均有不同程度降低（Ｐ＜０．０１）。结论母、儿的ＩＧＦⅠ分泌系统相对独立。ＩＧＦⅠ是调节胎儿生长发育的重要生长因子之一。     

胎儿宫内发育迟缓时孕妇及胎儿生长激素,胰岛素与甲状腺激素？…

目的 搪塞胎儿宫内发育迟缓（ＩＵＧＲ）时孕妇血清、脐血和羊水中生长激素、胰岛素及甲状腺激素的变化,方法 采用放射免疫和因相微球放射免疫法测定正常足月妊娠４２例（正常组）和足月妊娠ＩＵＧＲ２３例（ＩＵＧＲ）组）孕妇血清、脐血和羊水中生长激素、胰岛素、三碘甲腺原氨酸（Ｔ３）、甲状腺素（Ｔ４）和促甲状腺素（ＴＳＨ）水平。结果 ＩＵＧＲ组孕妇血清和脐血中生长激素显著下降,脐血和羊水中胰岛素水平与正常组比较     

胎盘表皮生长因子受体的表达改变与胎儿宫内生长迟缓 …

目的 研究胎儿宫内生长迟缓（ＩＵＧＲ）患者胎盘表皮生长因子受体（ＥＧＦＲ）的表达与正常妊娠及巨大儿胎盘之间是否有差异,并分析其变化与胎盘绒毛发育是否有关。方法 取足月分娩胎盘组织标本６３例,于分娩后立即置于４％中性甲醛缓冲液固定。用免疫组织化学ＳＰ法进行胎盘ＥＧＦＲ检测。同时对肖绒毛血管大小、面积及绒毛面密度等进行分析测量。结果 ＩＵＧＲ组胎盘ＥＧＦＲ的表达较正常对照组和巨大儿组明显增加,ＩＵＧＲ     

胰岛素样生长因子—I与胎儿出生体重的关系

目的 了解胰岛素生长因子－Ｉ（ＩＧＦ－Ｉ）在胎儿生长发育中所起的作用,方法 选择１７１例产妇及其所分娩的新生儿１６４例,根据出生体重将新生儿分为大于胎龄儿（ＬＧＡ）组,产妇７７例,新生儿６４例,适于胎龄儿（ＡＧＡ）组：产妇５９例,新生儿５９例;小儿胎龄儿（ＳＧＡ）组：产妇３５例,新生儿４３例,用放射免疫法测定血清中ＩＧＦ－Ｉ的浓度。结果 母血中ＩＧＦ－Ｉ浓度均高于脐血,两者间存在浓度梯度（Ｐ〈０．     

p53、bcl-2和bax基因表达与IUGR胎盘细胞凋亡的相关性研究

目的：研究胎儿宫内发育迟缓（ｉｎｔｒａｕｔｅｒｉｎｅ　ｇｒｏｗｔｈ　ｒｅｔａｒｄａｔｉｏｎ,ＩＵＧＲ)患者的胎盘细胞凋亡,以ｐ５３、ｂｃｌ－２和ｂａｘ相关性。方法：收集ＩＵＧＲ ２０份和正常足月分娩１２例的胎盘组织,应用原位末端标记(TUNEL)法检测其胎盘组织中的细胞凋亡,免疫组化法（ＩＨＣＡ）检测胎盘组织中ｐ５３、ｂｃｌ－２和ｂａｘ基因表达。结果：①正常和ＩＵＧＲ胎盘组织中均可见凋亡细胞,但ＩＵＧＲ胎盘中细胞凋亡指数（ａｐｏｐｔｏｓｉｓ　ｉｎｄｅｘ,ＡＩ）为１６．７～６８．３１,明显高于正常胎盘中的９．２～３０．４／高倍视野（平均２０．６７／高倍视野）,差异有显著性（Ｐ＜０．０５）;②ＩＵＧＲ ２０例胎盘组织中均有ｂａｘ过表达（４０％～９０％),高于正常组织（１０％～４０％）,差异有显著性（Ｐ＜０．０５）;③正常及ＩＵＧＲ胎盘组织中均未见ｂｃｌ－２表达;④ｐ５３在ＩＵＧＲ胎盘组织中的表达为５０％～８０％,而在正常组织中为５５％～８０％（Ｐ＞０．０５）;⑤ＩＵＧＲ２０例胎盘组织中细胞ＡＩ与ｂａｘ的表达呈正相关,与ｐ５３表达无关,ｂａｘ与ｐ５３之间无相关性。结论：①正常孕妇和ＩＵＧＲ患者胎盘组织中均有细胞凋亡,但ＩＵＧ     

Placental Vessel Morphometry in Growth Retardation and Increased Resistance of the Umbilical Artery Doppler Flow

Objectives: To study the tertiary-stem villi vessel lumen and wall thickness of placenta in pregnancy complicated with placental insufficiency and intrauterine growth retardation (IUGR), its correlation with the umbilical artery Doppler flow study, and compare with normal and non-IUGR pregnancies. Methods: Placentas from 45 deliveries (between 28 and 38 weeks) were collected for morphometric study of the tertiary-stem villi vessels. Each pregnancy had clinical suspicion of IUGR and was confirmed by serial ultrasound biometry, HC/AC ratio, and had abnormal umbilical artery Doppler velocimetry (RI). Each placenta was weighed after trimming of the membrane and the cord. Sections of the placenta (4μ.) were stained with hematoxylin and eosin and periodic acid-Schiff reagents. Tertiary-stem villi vessels were identified under a microscope (±40) and morphometric study was performed. Inner and outer circumferences (2.π.r) were measured, radii (r) were calculated, and vessel wall thickness was determined (outer r—inner r). These findings were compared with the findings from 78 placentas from normal pregnancies (between 28-40 weeks) and 27 placentas from pregnancies with medical complications without IUGR (non-IUGR) and with normal Doppler velocimetry (between 33 and 38 weeks).

Results: Weight of placentas were significantly (P < 0.005) lower in IUGR than the normal and non-IUGR groups. The vessel wall thickness was significantly (P < 0.0001) increased in IUGR group (mean 21.17 ± 3.16 μ [SD]) compared to normal and non-IUGR groups (mean 13.19 ± 1.66 μ). With advancing gestational age, the thicknesses of vessel walls in all groups were significantly (P < 0.001) decreased. There was significant (P < 0.001) decrease in lumen circumference in the IUGR group (mean 173 ± 31 μ) compared to normal and non-IUGR groups (mean 69 ± 23 u,). Significant (P < 0.001) correlation was observed between the thickness of a vessel wall and the increase in Doppler RI.

Conclusions: Pregnancies with growth retardation are associated with smaller placentas, increase in the thickness of tertiary-stem villi vessel wall, and decrease in lumen circumference. These changes are associated with an increase in the resistance index of the umbilical artery Doppler flow velocimetry.     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白3与胎儿生长发育的关系

目的:探讨胰岛素样生长因子1（IGF-1）及胰岛素样生长因子结合蛋白3（IGFBP-3）与胎儿生长发育的关系。方法:应用酶联免疫吸附试验（LISA）测定26例正常妊娠（正常组）,42例妊娠期糖尿病（GDM组）,20例胎儿宫内发育迟缓（IUGR组）孕妇足月剖宫产分娩时,母血与脐血中IGF-1及IGFBP-3的水平,同时记录3组孕妇的新生儿出生体重。结果:（1）母血IGF-1及IGFBP-3的水平正常组分别为18 6.81μg/L、22.82μg/L,GDM组为283.35μg/L、28.29μg/L,IUGR组为220.64μg/L、25.23μg/L,3组间 IGF-IN IGFBP.3水平差异均无显著性（P>0.05）;（2）脐血IGF-1及IGFBP-3的水平正常组分别为62.54μg/L、8.56μg/L,GDM组分别为83.74μg/L、10.21μg/L,IUGR组为37.94μg/L、7.82μg/L,分别进行3组间两两比较,3组IGF-1及IGFBP-3的差异均有显著性（P<0.01）;（3）新生儿平均出生体重正常组为3.22±0.32kg,GDM组为3.76±0.43kg,IUGR组为2.41±0.17kg,3组间两两比较,差异均有显著性（P<0.01）;（4）3组脐血IGF-1及IGFBP-3水平与新生儿出生体重均有显著性正相关（P<0.01）;（5）3组母血及脐血的IGF-1与IGFBP-3均呈显著性正相关（P<0.01）。结论:来自胎儿循环的IGF-1、IGFBP-3对胎儿的生长发育有重要的调节作用,可能参与巨大儿及IUGR的病     

Preliminary report of altered insulin secretion pattern in monochorionic twin pregnancies complicated with selective intrauterine growth restriction

Objective

Fetuses with intrauterine growth restriction (IUGR) have adaptive hormonal changes including changes in insulin, which may increase their future risks for developing diabetes mellitus. This study compared cord blood insulin concentrations in IUGR and appropriate for gestational age (AGA) fetuses in a monochorionic (MC) twin model.

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.     

Cord blood cortisol level is lower in growth-restricted newborns

AIM: To establish the difference in plasma cortisol concentrations between newborns with intrauterine growth-restricted (IUGR) and appropriate for gestational age (AGA) birthweights. SUBJECTS AND METHODS: We measured plasma cortisol concentrations in the umbilical venous cord blood of 68 IUGR newborns and 71 AGA birthweight newborns. All newborns were delivered in term, vaginally, in the morning, within 8 hours and had APGAR scores greater or equal to eight. RESULTS: There was no significant difference between compared groups according to maternal age, parity, gestational age and neonatal gender. Neonatal plasma cortisol levels were significantly lower in the IUGR (median: 312.3 mmol/L, min-max: 158.9-588.1 mmol/L) compared to the AGA group (median: 458.7 mmol/L, min-max: 314.5-718.5 mmol/L) (Mann-Whitney U-test; P<0000). The probability of having a cortisol plasma level greater than or equal to 458.7 mmol/L for IUGR newborns was only 1:12, and to have cortisol plasma level less than or equal to 312.3 mmol/L for AGA newborns was much lower (0:34). In the range of plasma cortisol level between 312.3 mmol/L and 458.7 mmol/L, no statistically significant difference in the plasma cortisol level between IUGR and AGA newborns was found. CONCLUSIONS: Neonatal plasma cortisol level is lower in the IUGR compared to the AGA group. Our results suggest that endocrine relationships seem to be lost in a specific group of the IUGR newborns. Although we usually tend to simplify the problem and declare only one cause, this time it is impossible. It is probable that the cause is hidden in small and insufficient placenta with deranged auto-regulation of placental 11beta-HSD-2 mechanism.     

Surface area of chorionic villi of placentas: an index of intrauterine growth restriction of fetuses

Aim:  Histomorphometric studies of placentas from idiopathic intrauterine growth restricted (IUGR) fetuses as well as normal-weight (control) fetuses were performed to determine surface area of chorionic villi (mostly terminal and few intermediate) using stereological technique. The results were compared to determine the difference in the values of surface area of chorionic villi, and to establish any relationship between placental histomorphometric changes and IUGR.
Methods:  Placentas from fifty (50) full-term, uncomplicated deliveries were collected; twenty eight (28) of them were associated with IUGR babies and twenty two (22) were from normal-weight babies. Placental weights and volumes were measured. Pieces of placental tissues were formalin-fixed, processed and embedded in paraffin. Seven-micron sections were cut and stained with HE stain. Histomorphometric and stereological studies were performed.
Results:  IUGR placental weights and volumes were lower than those of controls. Surface areas of villi of IUGR placentas had a mean of 8.19 m² (SD ± 2.88). For control placentas, the mean was 10.02 m² (SD ± 1.83). The mean value of the surface area of villi of the IUGR group was significantly lower than that of the control group.
Conclusion:  These findings pointed to a defect in the normal interaction between trophoblast and maternal tissue, leading to a reduced surface area of villi. Because the surface area of the villi presents the interface between maternal and fetal circulation, its reduction might be the cause of idiopathic intrauterine growth restriction.     

Placental microcirculation of intrauterine growth retarded fetuses: scanning electron microscopy of placental vascular casts

Aim The aim of this study is to investigate the ultra structural difference of placentas in IUGR fetuses that were all found to have abnormal umbilical artery Doppler waveforms.Methods Nine placentas from 7 IUGR fetuses and 2 from healthy normal fetuses were evaluated by scanning electron microscopy.Results All of the placentas of IUGR fetuses who had abnormal umbilical artery Doppler flow antenatally were found to have a prominent increase in the amount of total blood vessels; these aberrant blood vessels had a very tortuous course and they showed increased branching when compared with placentas from uncomplicated term pregnancies.Conclusions Our study showed that there is a clear difference in vascular ultra structure of the placentas of pregnancies with fetal growth restriction selected by abnormal umbilical artery Doppler flow test. IUGR seems to be a problem due to placental vascular insufficiency.     

The role of the anti-angiogenic factor endostatin in intrauterine growth restriction

OBJECTIVE: To study the impact of intrauterine growth restriction (IUGR) on anti-angiogenesis, by determining and comparing circulating levels of the potent anti-angiogenic factor endostatin, in full-term IUGR (under the 10th customized centile) and appropriate for gestational age (AGA) fetuses, neonates, as well as their mothers, granted that IUGR implies hypoxia and endostatin is down-regulated by the latter. METHODS: In 20 IUGR cases (mainly due to hypertension or preeclampsia) and 20 AGA controls we determined circulating endostatin levels, by enzyme immunoassay in the serum of mothers (MS), umbilical cords (UC-mixed arteriovenous blood)-representing the fetal state, and asymptomatic neonates on day 1 (N1) and 4 (N4) of life-signifying transition and stabilization to extrauterine life, respectively. RESULTS: Endostatin levels were significantly higher in AGA than IUGR UC, N1, and N4 (P <.0000, P = .0006, P = .024, respectively). Furthermore, UC endostatin levels positively correlated with the customized centiles of the infants (Spearman correlation coefficient 0.69, P = .00001). CONCLUSIONS: IUGR is characterized by lower circulating endostatin concentrations in the fetus and neonate, possibly because under lower oxygen concentrations an unbalanced state of angiogenesis stimulators versus inhibitors takes place.     

胎儿宫内生长迟缓孕妇静脉血及其新生儿脐血一氧化氮水平测定的临床意义

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