子痫前期患者与新生儿脐带血中IGF-I及GH水平分析(附30例报告)

选择子痫前期患者30例(研究组)及同期住院单胎妊娠、无内外科并发症32例孕妇(对照组)为研究对象,用放射免疫法测定两组孕妇血清及新生儿脐静脉血清中胰岛素样生长因子-Ⅰ(IGF-I)及生长激素(GH)的水平,并观察两组新生儿体重与胎盘重量及其与前两者之间的相关性。结果研究组新生儿体重及胎盘重量均明显低于对照组,孕妇血清及脐血中IGF-I均低于对照组;两组母血与脐血IGF-I水平均呈正相关;两组新生儿出生体重及胎盘重量均与母血GH水平呈正相关;研究组新生儿体重与脐血GH呈负相关、在对照组则无相关性,胎盘重量在两组间与脐血GH均无相关性。认为子痫前期状态下孕妇及胎儿体内IGF-I及GH水平改变与胎儿生长发育有关。     

胰岛素-胰岛素样生长因子代谢轴在胎儿生长发育中的作用

目的探讨胰岛素-胰岛素样生长因子（IGF）代谢轴在胎儿宫内生长发育中的作用。方法连续收集266名单胎足月新生儿基本资料,采用放免法检测脐血胰岛素和IGF水平。结果（1）脐血胰岛素水平与出生体重、BMI、身长和胎盘重量均呈正相关（P〈0．01）。（2）脐血IGF水平与出生体重、BMI、身长和胎盘重量均呈正相关（P〈0．01）。（3）脐血胰岛素水平和IGF水平呈显著正相关（P〈0．01）。结论脐血胰岛素、IGF水平可作为评价胎儿宫内生长发育情况的参考指标。     

子痫前期患者与新生儿脐带血中IGF-Ⅰ及GH水平分析（附30例报告）

选择子痫前期患者30例（研究组）及同期住院单胎妊娠、元内外科并发症32例孕妇（对照组）为研究对象，用放射免疫法测定两组孕妇血清及新生儿脐静脉血清中胰岛素样生长因子-Ⅰ（IGF-Ⅰ）及生长激素（GH）的水平，并观察两组新生儿体重与胎盘重量及其与前两者之间的相关性。结果研究组新生儿体重及胎盘重量均明显低于对照组，孕妇血清及脐血中IGF-Ⅰ均低于对照组；两组母血与脐血IGF—Ⅰ水平均呈正相关；两组新生儿出生体重及胎盘重量均与母血GH水平呈正相关；研究组新生儿体重与脐血GH呈负相关、在对照组则元相关性，胎盘重量在两组间与脐血GH均元相关性。认为子痫前期状态下孕妇及胎儿体内IGF—Ⅰ及GH水平改变与胎儿生长发育有关。     

锌对胎儿生长发育影响的临床研究

为探讨锌与胎儿生长发育的关系,将66例新生儿按出生体重分为小于胎龄儿组（SGA组,出生体重小于同胎龄正常标准体重的第10百分位）及适于胎龄儿组（AGA组,出生体重在同胎龄正常标准体重的第10－90百分位）,分别测定两组脐血中锌含量及胰岛素生长因子－1（IGF－1）,胰岛素样生长因子结合蛋白－3（IGFBP－3）水平。结果显示,SGA组脐血锌含量及IGF－1、IGFBP－3水平均显著降低,与AGA组比较有显著差异（P均＜0．01）;锌浓度随出生体重和胎龄的增加而增加（P均＜0．01）,与IGF－1,IGFBP－3水平呈正相关（P均＜0．01）。认为胎儿发育与体内锌含量密切相关,缺锌可导致胎儿宫内发育迟缓,胎儿母亲孕期应适量补锌。     

宫内发育迟缓与胰岛素样生长因子及其结合蛋白关系的研究

为探讨宫内发育迟缓（IUGR）的发生机制,检测了86例新生儿脐血胰岛素样生长因子－1（IGF－1）、胰岛素样生长因子结合蛋白－3（IGFBP－3）水平,并分析上述指标变化与胎儿期生长的关系。将86例新生儿分为两组,IUGR（即小于胎龄儿）组22例,适于胎龄儿（AGA）组64例,采用竞争性放射免疫分析法（RIA）测定两组脐血IGF－1水平,非竞争性免疫放射分析法（IRMA）测定IGFBP－3水平。结果显示,与AGA组相比,IUGR组脐血IGF－1和IGFBP－3水平显著降低（P＜0．001）;IGF－1水平随胎龄及出生体重增加而增加（P＜0．01）;IGFBP－3水平与胎龄及出生体重呈相关（P＜0．01）;IGF－1与IGFBP－3呈正相关（P＜0．01）。认为IUGR与IGF－1及其结合蛋白密切相关,不论何种原因引起的IUGR,其脐血IGF－1、IGFBP－3水平均低,IGF－1水平下降与IGFBP－3下降相伴随;脐血IGF－1、IGFBP－3水平与胎龄及出生体重呈正相关,随着胎龄的增加和出生体重的增长,IGF－1、IGFBP－3水平不断升高。     

新生儿脐血血脂水平及胎心率检测分析

目的探讨新生儿脐血血脂水平及胎心率的变化。方法选取头胎顺产新生儿87例,测定小于胎龄儿(SGA)14例、适于胎龄儿(AGA)63例、大于胎龄儿(LGA)10例脐血血脂水平,记录胎儿娩出前5 min胎心率。并使用全自动生化分析仪测定脐血甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和载脂蛋白AI(ApoAI)和载脂蛋白B(ApoB)水平。结果SGA组脐血TG、TC、LDL-C、ApoB水平均高于AGA组和LGA组,HDL-C、ApoAI水平低于AGA组和LGA组,差异有统计学意义(P<0.05);新生儿血脂指标与胎心率回归分析未发现明显相关性(P>0.05)。结论不同的宫内环境引起胎儿代谢的改变,胚胎生长受限的新生儿存在血脂代谢障碍。     

脐带血瘦素水平与胎儿宫内生长发育的关系

目的探讨瘦素在胎儿宫内生长发育中的作用,为代谢疾病的早期干预提供实验依据。方法连续入选2009年7月至2010年1月在北京协和医院出生的单胎足月新生儿266名（男婴140名,女婴126名）,留取脐带血,出生后立即测量新生儿体重、身长、头围及胎盘重量。根据出生体重将新生儿分为低出生体重组（n=58,男婴25例,女婴33例）、正常出生体重组（n=180,男婴99名,女婴81名）和高出生体重组（n：28,男婴16例,女婴12例）。采用放射免疫分析法测定脐带血瘦素水平。采用独立样本t检验、Pearson相关分析、多元线性回归分析进行数据统计。结果与正常出生体重组[（9±5）μg/L]相比,低出生体重组脐带血瘦素水平[（7±5）μg/L]明显降低（t=3．216,P〈0．05）,高出生体重组[（15±7）μg／L]明显升高（t=-4．026,P〈0．01）。女婴脐带血瘦素水平[（11±6）μg/L]明显高于男婴[（8±5）μg／L,t=一3．800,P〈0．01]。Pearson相关分析显示,脐带血瘦素水平与新生儿出生体重、身长、体质指数和胎盘重量呈显著正相关（r值分别为0．391、0．280、0．361、0．323,均P〈0．01）。校正母亲年龄、妊娠前体质指数、新生儿性别和胎龄后,脐带血瘦素水平仍与出生体重呈直线正相关（r2=0．289,P〈0．01）。结论脐带血瘦素水平与新生儿出生体重呈正相关,有望作为反映新生儿宫内生长发育的一个客观指标。     

脐血促红细胞生成素、内皮素与围产儿缺氧的关系

目的 探讨脐血促红细胞生成素（EPO）、内皮素（ET-1）与围产期胎儿、新生儿缺氧的关系。方法 采用ELISA法检测新出生54例高危儿脐血EPO与ET-1,并与14例健康顺产儿进行对照。结果 羊水Ⅲ度浑浊组及先兆子痫／子痫组脐血EP0水平较对照组明显升高（P〈0．01）。新生儿窒息组ET-1水平高于对照组（P〈0．01）。先兆子痫／子痫组脐动脉血pH值与正常顺产组脐动脉血pH值差异显著（P〈0．01）。先兆子痫／子痫组EPO水平与pH水平显著负相关（r=-0．984,P〈0．01）。新生儿窒息组脐血ET-1水平与5min Apgar评分值呈显著负相关（r=-0．9,16,P〈0．01）。结论 脐血EPO在提示围产儿亚急性、慢性缺氧．ET-1在提示围产儿急性缺氧方面具有重要的作用。     

未成熟儿的护理诊断与护理措施

未成熟儿是指胎龄在28～37周内娩出的体重小于2500g、身长不足47cm的新生儿。由于未成熟儿各个器官组织发育不健全,生理功能低下,所以病死率高。1 临床资料 自2000年以来,在我院共出生新生儿2461人,其中未成熟儿64例,占2.42％。胎龄29～36~(+6)周,平均胎龄34.5周。     

未成熟儿的护理诊断与护理措施

未成熟儿是指胎龄在28～37周内娩出的体重小于2500g、身长不足47cm的新生儿。由于未成熟儿各个器官组织发育不健全,生理功能低下,所以病死率高。1 临床资料 自2000年以来,在我院共出生新生儿2461人,其中未成熟儿64例,占2.42％。胎龄29～36~( 6)周,平均胎龄34.5周。     

Umbilical cord ghrelin concentrations in small- and appropriate-for-gestational age newborn infants: relationship to anthropometric markers

Ghrelin is a newly discovered orexigenic peptide originating from the stomach. Circulating ghrelin levels reflect acute and chronic energy balance in humans. However, it is not known whether ghrelin also plays a role in energy homeostasis during fetal life. Forty-one small-for-gestational age (SGA) and 34 appropriate-for-gestational age (AGA) infants were studied in order to determine whether cord blood ghrelin concentrations were different in SGA infants compared with AGA infants and the relationship to anthropometric measurements at delivery. The cord blood ghrelin concentrations of SGA infants (means+/-S.E.M.; 15.20+/-3.08 ng/ml) were significantly greater than of AGA infants (2.19+/-0.24 ng/ml) (P<0.0001). They were negatively correlated with the infants' birth weights (r=-0.481, P<0.0001) and with body mass index values (r=-0.363, P<0.001). The higher ghrelin concentrations were found in female infants (20.42+/-4.55 ng/ml) than in males (7.05+/-2.27 ng/ml) in the SGA group (P=0.042). These data provide the first evidence that cord ghrelin levels of SGA infants are greater than those of AGA infants and it is suggested that ghrelin is also affected by nutritional status in the intrauterine period.     

Ghrelin concentration in cord and neonatal blood: relation to fetal growth and energy balance

To investigate the relationship between ghrelin and both fetal and neonatal growth parameters and energy balance, we measured plasma ghrelin concentrations in 54 cord blood samples (male, n = 34; female, n = 20; gestational age, 37.0-41.6 wk; birth weight, 2206-4326 g) and 47 neonatal blood samples (male, n = 27; female, n = 20; postnatal d 3-8). The plasma ghrelin concentrations in cord blood ranged from 110.6-446.1 pmol/liter (median, 206.7 pmol/liter), which were equal to or higher than those in normal weight adults. These values were inversely correlated with birth weight (r = -0.40; P = 0.002), birth length (r = -0.36; P = 0.007), placental weight (r = -0.35; P = 0.01), and IGF-I concentration (r = -0.49; P = 0.0002), but were not significantly correlated with the GH concentration (r = 0.22; P = 0.12). The ghrelin concentrations in small for gestational age newborn were significantly higher than those in appropriate for gestational age newborns (P = 0.0008). The ghrelin concentrations in the vein were significantly higher than those in the artery in 8 cord blood samples (P = 0.01), which suggests that the placenta is an important source of fetal ghrelin. In neonates, the ghrelin concentrations ranged from 133.0-481.7 pmol/liter (median, 268.3 pmol/liter), which were significantly higher than those in cord blood (P < 0.0001). These results suggest that ghrelin may contribute to fetal and neonatal growth.     

Low cord ghrelin levels in term infants are associated with slow weight gain over the first 3 months of life

Lower ghrelin levels have been related to slower growth in small for gestational age infants, and infants with higher cord leptin levels have been reported to gain weight more slowly from birth to 2 yr. This study investigated whether cord blood ghrelin and leptin levels are related to weight gain up to 12 wk of age. One hundred infants were weighed at birth and at 12 wk, and cord blood was assayed for ghrelin and leptin. The mean (+/-sd) birth weight was 3.458 (0.433) kg (median, 3.390; range, 2.510-4.615 kg). The mean (+/-sd) leptin level was 10.1 (6.7) ng/ml (median, 8.4; range, 1.6-36.7 ng/ml), and that of ghrelin was 760.9 (282.9) pg/ml (median, 770; range, 210-1670 pg/ml). Higher birth weight was associated with slower weight gain. Leptin was correlated with birth weight, but ghrelin was not, and leptin and ghrelin levels were not significantly correlated with one another. With birth weight as a control variable, ghrelin was significantly associated with slow weight gain (chi(2) = 7.20 with 1 df; P < 0.01), although leptin was not (chi(2) = 1.59 with 1 df; P > 0.1). In conclusion, lower cord ghrelin levels are associated with slower weight gain from birth to 3 months of age.     

Circulating levels of ghrelin in human fetuses

OBJECTIVE: Ghrelin is a GH secretagog isolated recently from rat stomach and involved in the stimulation of food intake and adiposity in rodents and humans. Moreover, subsequent studies showed that ghrelin is expressed in rat and human placenta, suggesting a possible influence of the peptide on fetal growth. The aim of this study was to evaluate circulating levels of ghrelin in appropriate for gestational age (AGA) or intrauterine growth-restricted (IUGR) fetuses. SUBJECTS AND METHODS: Ghrelin levels between 20 and 39 weeks of gestation were measured in 16 AGA and nine IUGR fetuses in whom blood was collected by cordocentesis performed for prenatal diagnosis of different diseases or during elective cesarean section. In most samples, GH, cortisol and leptin levels were also evaluated. Results are expressed as means+/-S.D. Differences were tested using the Student's t-test with Welch correction. P<0.05 was considered significant. RESULTS: All fetuses showed levels of ghrelin in the umbilical venous blood (100+/-99 pmol/l) that did not correlate with the gestational age or the maternal ghrelin levels. No difference was found between umbilical venous and arterial concentrations, suggesting that fetal tIssues are a source of ghrelin. Ghrelin levels in IUGR fetuses were significantly higher than those found in AGA fetuses (176+/-125 vs 58+/-44 pmol/l; P<0.005). Moreover, in samples obtained at birth, ghrelin concentrations correlated negatively with birth weight (P<0.05). In IUGR fetuses, GH and cortisol concentrations were higher and leptin levels lower than in AGA fetuses, although no significant correlation between these parameters and ghrelin levels was found. CONCLUSION: The presence of ghrelin in the fetal circulation as well as its increase in IUGR fetuses suggest a role of this peptide during intrauterine development.     

Cord plasma concentrations of adiponectin and leptin in healthy term neonates: positive correlation with birthweight and neonatal adiposity

OBJECTIVE: Adiponectin is negatively associated with leptin, insulin and obesity in children and adults. Whereas increases in fetal insulin and leptin are associated with increased weight and adiposity at birth, the role of adiponectin in fetal growth has not yet been determined. The aims of this study were to examine the relationships between adiponectin and insulin, leptin, weight and adiposity at birth in healthy term infants. DESIGN AND METHODS: Anthropometric parameters including weight, length, circumferences and skinfold thickness were measured, and plasma lipid profiles, insulin, leptin and adiponectin concentrations in cord blood samples from 226 singleton infants born at term after uncomplicated pregnancies were assayed. RESULTS: Cord plasma adiponectin, leptin and insulin levels correlated significantly and positively with birthweight (P = 0.001, P < 0.001, P < 0.001, respectively) and the sum of skinfold thicknesses (P < 0.001, P < 0.001, P < 0.001, respectively). Mean cord plasma adiponectin and leptin levels, but not insulin level, were significantly higher in large-for-gestational-age (LGA) infants compared with appropriate-for-gestational-age (AGA) infants. Cord plasma leptin concentration, but not adiponectin concentration, was significantly higher in female infants than in male infants (P = 0.003 and P = 0.94, respectively). Cord plasma adiponectin concentration correlated positively with leptin level (P = 0.007) but not with insulin level (P = 0.78). CONCLUSIONS: High adiponectin levels are present in the cord blood. Cord plasma adiponectin and leptin levels are positively correlated with birthweight and adiposity. This suggests that adiponectin may be involved in regulating fetal growth.     

Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation

The octanoylation of Ser3 is essential for the biological function of ghrelin. We examined the concentrations of the n-octanoylated active-form ghrelin in cord and neonatal blood using an RIA system that specifically recognized n-octanoylated ghrelin, as well as a system that measured the total ghrelin concentration. Plasma levels of active ghrelin in cord blood ranged from 7.7 to 38.4 pmol/l and correlated excellently with those of total ghrelin (r = 0.81, p<0.0001). The active ghrelin/total ghrelin (A/T) ratio ranged from 0.038 to 0.12 (median 0.072). The active ghrelin concentrations negatively correlated with birth body weight (r = -0.34, p = 0.01) and IGF-1 concentrations (r = -0.40, p = 0.003), but did not correlate with growth hormone (GH) concentrations. A considerable level of active ghrelin was detected in premature newborns. Venous cord blood samples showed a significantly higher active ghrelin concentration (p = 0.03) and A/T ratio (p = 0.01) than those in the artery. In neonatal blood, active ghrelin concentrations ranged from 4.6 to 22.6 pmol/l and the A/T ratio ranged from 0.02 to 0.081. These results demonstrate the existence of active-form ghrelin in fetal and neonatal circulation and may suggest the energy supply-dependent regulation of ghrelin expression/secretion in utero.     

Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake

CONTEXT: Ghrelin, a natural GH secretagogue, is mainly characterized by nonendocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated with insulin secretion, enhanced in anorexia, and reduced in obesity. Ghrelin levels in newborns were shown to be similar to those found in children and adults without any gender-related difference. OBJECTIVE: The aim of this study was to evaluate ghrelin variations in preterm newborns as a function of fasting and feeding. METHODS: To this end, in 31 preterm neonates (13 males and 18 females) categorized as appropriate for gestational age, total ghrelin levels were measured in cord blood and then on the fourth day of life before and after meals. RESULTS: Ghrelin levels in cord blood [(median 25th-75th centile) 184; 122-275 pg/ml] were higher (P < 0.006) than levels measured in the mothers at delivery (167.0; 89-190 pg/ml). In newborns on the fourth day of life, ghrelin levels in fasting conditions (451; 348-649 pg/ml) were higher (P < 0.0004) than those in cord blood. The meal did not at all modify ghrelin levels (476; 302-775 pg/ml), which were unchanged, compared with those in fasting condition. Total ghrelin levels in cord blood were not associated with weight and length; conversely, on the fourth day of life ghrelin levels in newborns were negatively correlated to birth weight as well as the present weight (P = 0.05, r = -0.4). Ghrelin levels were independent of gender, type of delivery, and the kind of feeding regimen. CONCLUSIONS: The secretion of total ghrelin increases from delivery to the fourth day of life when it is refractory to the inhibitory effect of food intake, but it is negatively correlated to body weight.     

Plasma ghrelin and resistin concentrations are suppressed in infants of insulin-dependent diabetic mothers

This study aimed to investigate 1) the effect of maternal diabetes mellitus on ghrelin, resistin, leptin, and insulin in term newborns; 2) the interrelationship of these metabolic hormones in the early postnatal period; and 3) the association of the hormones with anthropometric parameters at birth. A total of 120 term newborns were prospectively enrolled and categorized into three groups: 40 were infants of nondiabetic mothers (group N), 42 were infants born to mothers with gestational diabetes on low energy dietary treatment (group D), and 38 were infants born to mothers with preexisting or severe gestational diabetes who required exogenous insulin for stabilization of blood sugar during pregnancy (group I). Plasma ghrelin and resistin were significantly lower in group I than in either group N or group D infants (P < 0.048). Plasma ghrelin and subscapular skinfold thickness were significantly higher in female than in male infants [plasma ghrelin: median (interquartile range), 3.8 (3.0-4.8) vs. 3.0 (2.4-4.0) ng/ml in females and males, respectively; P = 0.003; subscapular skinfold thickness: 4.9 (4.2-5.6) vs. 4.6 (3.9-5.2) mm; P = 0.03]. In group N, plasma ghrelin was significantly, but negatively, associated with birth weight (r = -0.31; P = 0.05) and body length (r = -0.33; P = 0.04), whereas in group I, plasma ghrelin was negatively correlated with plasma resistin (r = -0.37; P = 0.02). Plasma ghrelin and resistin are suppressed in infants of insulin-dependent diabetic mothers, suggesting that the metabolic hormonal system is probably operational in fetal and early postnatal life. A low circulating ghrelin concentration may be advantageous to these infants, because a reduction in appetite may prevent excessive weight gain postnatally and counterbalances the in utero anabolic effect of hyperinsulinism in poorly controlled diabetic mothers. The suppressive effect of insulin on resistin may partially explain the excess accumulation of adipose tissue in infants of diabetic mothers by reducing the inhibitory effect of resistin on adipogenesis. Female infants have significantly higher plasma ghrelin levels than male infants, suggesting that sexual dimorphism exists in utero. This study has also shown an association between some of the metabolic hormones in specific groups of infants and thus suggests that these hormones could have interacted in utero to regulate growth and fat storage during this critical period.     

Fetal insulin-like growth factor (IGF)-I, IGF-II, and ghrelin in association with birth weight and postnatal growth in monozygotic twins with discordant growth

OBJECTIVE: To investigate the relative contribution of genetic (fetal) vs. environmental (maternal/placental) factors on growth, we studied monozygotic twins with intertwin birth weight difference. PATIENTS AND METHODS: Twenty-seven twins (15 with discordant growth) who have been treated for severe twin-to-twin transfusion syndrome by laser coagulation were studied. Cord blood samples were analyzed for IGF-I, IGF-II, IGF-binding protein-2, and ghrelin. Intertwin difference (Delta) of birth weight was correlated to Delta of the parameters analyzed. The Delta weight after 1 yr was correlated with Delta birth weight and all hormones. RESULTS: The Delta birth weight was positively correlated with Delta IGF-I (r = 0.66; P < 0.0002) and negatively correlated with Delta IGF-binding protein-2 levels (r = -0.68; P < 0.001) but with neither Delta IGF-II nor Delta ghrelin. There was a strong intertwin correlation for all hormones. By comparing the growth in the first year, we found an overall reduction of the relative weight difference between the twins of 57%. ANOVA was used to calculate factors for prediction of postnatal catch-up growth. Besides the birth weight difference (R2= 0.84; P < 0.0001), only ghrelin was of prognostic value for postnatal catch-up growth (R2= 0.94; P = 0.0035). CONCLUSION: These data confirm the importance of IGF-I in contrast to IGF-II for fetal weight. Additionally, ghrelin seems to be involved in fetal and probably postnatal growth.     

Ghrelin in neonatal rats: distribution in stomach and its possible role

Ghrelin, a 28 amino acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. The fact that administration of ghrelin, centrally or peripherally, stimulates both food intake and GH secretion suggests that stomach ghrelin has an important role in the growth of rats. We used immunohistochemistry and radioimmunoassay to determine the age at which ghrelin-immunostained cells begin to appear in the rat stomach. Ghrelin-immunoreactive cells were found to be expressed in the fetal stomach from pregnancy day 18. The number of ghrelin-immunoreactive cells in the fetal stomach increased as the stomach grew. The amount of ghrelin in the glandular part of the rat stomach also increased, in an age-dependent manner, from the neonatal stage to adult. Eight hours of milk restriction significantly decreased the ghrelin concentration in the stomachs of 1-week-old rats, and increased the ghrelin concentration in their plasma. Administration of ghrelin to 1- and 3-week-old rats increased plasma GH concentrations. The daily subcutaneous administration of ghrelin to pregnant rats from day 15 to day 21 of pregnancy caused an increase in body weight of newborn rats. In addition, daily subcutaneous administration of ghrelin to neonatal rats from birth advanced the day of vaginal opening from day 30.7+/-0.94 to day 27.9+/-0.05. These results suggest that ghrelin may be involved in neonatal development.