糖尿病和心血管病家族史与胎儿宫内发育及新生儿胰岛素敏感性的关系

目的　探讨胎儿发育受限与成人期冠心病、高血压、2型糖尿病之间的联系是否与遗传基因有关。　方法　选取小于胎龄儿75例,适于胎龄儿224 例。均进行出生测量,记录父母及祖父母是否患有2型糖尿病、冠心病、高血压(母亲糖尿病除外),并于生后第3 天测定餐前血糖和胰岛素水平。　结果　小于胎龄儿组家族中冠心病、高血压、糖尿病的发生率分别为20. 0%、30. 7%和12.0%,显著高于适于胎龄儿组的9.3%、14.7%和3.5%(P<0.01)。与家族史阴性新生儿相比,一种疾病家族史阳性时,发生小于胎龄儿的相对危险度为OR=2.788;95%CI:1.517~5.124。任意两种或三种疾病家族史均阳性时,发生小于胎龄儿的相对危险度为OR= 3. 955; 95%CI: 1. 572 ~9.951。对孕周、出生体重及产时Apgar评分校正后,家族史阳性新生儿与家族史阴性新生儿相比血糖水平差异无统计学意义(P>0.05),但胰岛素/血糖比值则明显增高(P<0.05)。　结论　遗传基因在宫内发育受限及宫内发育受限儿成人后冠心病、高血压和糖尿病的发病过程中很可能起一定作用。     

胎儿生长受限大鼠胰岛素敏感性的动态变化

目的 探讨胎儿生长受限(fetal growth restriction,FGR)大鼠胰岛素敏感性的变化规律.方法 母鼠受孕后第1天始随机分为对照组和低蛋白组,各10只.低蛋白组孕鼠采用低蛋白饮食法建立FGR模型.低蛋白组仔鼠中出生体重低于对照组仔鼠平均出生体重两个标准差者定为FGR鼠.测定对照组和FGR仔鼠(每组雌雄各8只)生后3、7、14、30、60及90 d空腹血浆血糖(fasting plasma glucose,FPG)及空腹血清胰岛索(fasting serum insulin,FINS),计算胰岛素抵抗指数及胰岛素敏感指数.90 d时测定血甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和糖化血红蛋白,同时行腹腔葡萄糖耐量实验.结果 (1)低蛋白组仔鼠平均出生体重为(4.92±0.36)g,低于对照组的(6.43±0.59)g,差异有统计学意义(t=14.73,P＜0.05).(2)雄性FGR鼠生后60 d时FPG高于对照组[(9.38±1.57)mmol/L与(5.58士1.24)mmol/L],直至90 d[(8.95±1.83)mmol/L与(6.21±1.14)mmol/L],差异有统计学意义(t=-3.291,P＜0.05);雌性FGR鼠90 d时FPG为(9.08±1.65)mmol/L,高于对照组的(6.73土0.67)mmol/L,差异有统计学意义(t=-3.226,P＜0.05);雄性FGR鼠FINS 30 d时开始高于对照组,直至90 d时;雌性FGR鼠60及90 d时FINS 高于对照组,差异均有统计学意义(P＜0.05);雄性及雌性FGR鼠胰岛素抵抗指数及胰岛素敏感指数分别于30 d及60 d始与对照组相比出现改变,直至90 d,差异有统计学意义(P均＜0.05).腹腔葡萄糖耐量实验结果显示,从0 min始各时间点雄性和雌性FGR鼠血糖均高于对照组,差异均有统计学意义(P＜0.05).(3)生后90 d时,雄性FGR鼠糖化血红蛋白为(7.03±0.54)%,高于对照组的(4.37±0.64)%,差异有统计学意义(t=-8.028,P＜0.05).无论雄性或雌性仔鼠,2组血脂水平差异均无统计学意义(P均＞0.05).结论 FGR鼠在生后早期尚能维持正常的FPG和FINS水平,随着日龄增加,胰岛素敏感性从青年期逐渐降低,直至成年期,而且雄性FGR鼠更易发生胰岛素抵抗.

Abstract：

Objective To investigate the regular pattern of dynamic changes of insulin sensitivity in fetal growth restriction (FGR) rats. Methods Twenty pregnant female rats were randomly divided into two groups as normal-protein group (NP) and low-protein group (LP), which respectively received normal protein diet (20% protein) and low protein diet (8% protein) during pregnancy. Weights of newborns were measured within 6 hours after birth, and the LP offspring whose birth weights were at least 2 standard deviations below the mean of NP offspring (≤2 standard deviations) were defined as FGR rats. At day 3, 7, 14, 30, 60 and 90 after birth, rats were fasted for 12 hours and then angular vein blood was collected to measure fasting plasma glucose (FPG) and fasting serum insulin (FINS) level. At 90 days of age, intraperitoneal glucose tolerance test (IPGTT)was performed; and blood triglyceride ( TG ), low-density lipoprotein cholesterol ( LDL-C ),high-density lipoprotein cholesterol (HDL-C) and glycosylated hemoglobin Alc (HbAlc) were measured. Insulin sensitivity was evaluated by FINS, insulin resistance index (HOMA-IR), insulin sensitivity index (ISI) and IPGTT. Results (1) Birth weights of LP offspring [(4. 92 ± 0. 36) g]were significantly lower than those of NP ones [(6. 43 ± 0. 59) g] (t = 14. 73, P＜0. 05). The incidence of FGR in LP was 88. 2% ; and for the male and female rats, the FGR rate was 94. 1% and 83. 1%, respectively. (2) FPG levels in the male FGR rats were significantly higher than in the NP from the age of 60 days [(9.38 ± 1.57) mmol/L vs (5. 58 ± 1.24) mmol/L] to 90 days [(8. 95 ±1.83) mmol/L vs (6. 21± 1.14) mmol/L] (t=-3. 291, P＜0. 05), while FPG levels in female FGR rats increased significantly only at 90 days of age [(9. 08±1.65) mmol/L vs (6.73±0. 67) mmol/L](t=-3. 226,P＜0. 05). FINS levels were significantly higher in FGR rats than in the NP from the age of 30 days (male FGR rats) or 60 days (female FGR rats) to 90 days (P＜0. 05, respectively).Similarly, HOMA-IR was significantly higher in FGR rats than in the NP at the age of 30 days (male FGR rats) or 60 days (female FGR rats) to 90 days (P＜0. 05, respectively). ISI in male FGR rats showed a reduction in comparison with the NP from the age of 30 to 90 days, while as to the female FGR rats it was significantly lower than in the NP only at 60 days of age and continued to 90 days (P＜0. 05, respectively). IPGTT showed that after injection of glucose, blood glucose at all four points (from 0 min to 120 min) in both male and female FGR rats were higher than that in the NP (P＜0. 05). (3) No significant difference was observed in TG, LDL-C and HDL-C at 90 days of age between the FGR rats and NP ones, while HbA1c in the male FGR rats was significantly higher than that in the NP [(7. 03±0. 54) % vs (4. 37±0. 64)%,t= -8. 028, P＜0. 05]. Conclusions FGR rats are able to maintain glucose balance and normal insulin levels during their earlier age, while insulin sensitivity decreased from adolescence to adulthood. The change of insulin sensitivity is different between male and female FGR rats, and male FGR rats are more likely to develop insulin resistance.     

胎儿生长受限的筛查

胎儿生长受限危害胎儿存活及健康,越来越受到围产工作者的关注,胎儿生长受限的筛查有助于针对筛查高风险孕妇加强监护,降低晚孕期死胎、死产和新生儿死亡。文章就目前胎儿生长受限筛查的意义和常见的筛查方法及进展作一综述。     

胎儿生长受限的围分娩期监测

文章以国内外指南、临床研究及专家共识为基础,阐述胎儿生长受限是胎儿生长体重低、临床上伴有胎盘以及脐带血流异常,介绍了围产期采用彩色多普勒各项指标检测的意义,以及各指标的临床应用价值,探讨了降低胎儿生长受限的围分娩期不良结局相关措施。     

晚孕期脑胎盘率预测胎儿不良结局的研究进展

产前有效预测胎儿围生期不良结局,及时采取干预措施对降低围生期发病率和死亡率,改善胎儿及新生儿预后有重大意义。目前常用的产前监测方法主要有胎儿电子监护、胎儿生物物理评分和超声多普勒评估等,其中超声多普勒作为产前最常用的监测方法,其预测胎儿围生期不良结局的应用价值成为了当下众多学者研究的热点。近年来一些学者发现晚孕期脑胎盘率(cerebroplacental ratio, CPR)能够预测围生期不良结局,尤其针对于生长受限的胎儿预测效果显著,现阐述晚孕期CPR在预测胎儿不良结局方面的应用进展。     

胰岛素样生长因子-Ⅱ与胎儿生长迟缓的探讨

胎儿宫内生长迟缓 (IU GR)可引起胎儿在围产期和长期发育的异常 ,这些异常甚至终生受害 ,不可逆转 ,从而严重影响了人类素质 [1 ]。近年来 ,许多学者对IUGR的病因进行了广泛的研究 ,尤其是生长因子对调节胎儿生长发育方面的研究十分活跃。本研究旨在通过测定母血、脐血和胎盘组织的胰岛素样生长因子 - (IGF- )浓度来探讨 IUGR与IGF- 关系。一、资料与方法1.资料来源与分组 :(1)对照组 :正常非妊娠妇女 30例 ,为我院门诊健康女性婚前检查者 ,平均年龄 (2 3.5± 2 .8)岁。 (2 )正常体重儿组 :30例 ,为我院1998年 7月至 1999年 1月…     

关注胎儿生长受限诊治细节，彰显“求同存异”

        胎儿生长受限（fetal growth restriction,FGR）是产科常见的并发症之一,其发病率在世界各地有很大的差异：在发达国家和地区中FGR发病率为6%～9%［1］,而在中、低收入国家和地区中FGR发病率可高达19.3%［2］。来自中国22个省、自治区、直辖市的调研数据显示,我国FGR的发病率为6%～13%［3］。由此可见,FGR不仅是发达地区更是经济落后地区所面临的母婴健康重大挑战。 浏览更多请关注本刊微信公众号及当期杂志。     

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     

胎儿生长受限与成年胰岛素抵抗的研究进展

胎儿生长受限（fetal growth restriction，FOR），以前也称胎儿宫内发育迟缓（intrauterine growth retardation，IU—OR），是指胎儿出生体重低于相应孕周平均体重第10百分位数或低于平均体重两个标准差。近年来国内外研究表明FOR不仅影响胎儿期和儿童期的智力体格发育，成年后由于机体胰岛素抵抗（insulin resistance，IR）导致代谢综合征（包括2型糖尿病、高血压、高血脂、冠心病等）的易感性也明显增加。[第一段]     

应用硫酸镁治疗胎儿生长迟缓

目的　探讨胎儿生长迟缓 (intrauterinegrowthretardation ,IUGR)孕妇的静脉血与新生儿脐静脉血中镁离子含量的变化及其与新生儿体重的关系。方法　将 39例IUGR孕妇随机分为治疗 1组 14例 ,治疗 2组 14例 ,未治疗组 11例。治疗 1组用 10 %葡萄糖 5 0 0ml 复方丹参液 14ml 低分子右旋糖酐 5 0 0ml静脉滴注 ;治疗 2组除有与治疗 1组相同的处方外 ,再加用 5 %葡萄糖 5 0 0ml 2 5 %硫酸镁 2 0ml静脉滴注 ,并以同期分娩的 12例正常孕妇为对照组。采用全自动生化分析仪 ,测定 4组孕妇的肘静脉血和新生儿脐静脉血中的镁离子含量。结果　治疗 1组孕妇静脉血中镁离子含量[(0 6 9± 0 0 5 )mmol/L]和未治疗组 [(0 6 8± 0 0 2 )mmol/L]比较 ,差异无显著性 (P >0 0 5 ) ,和治疗 2组 [(1 0 6± 0 0 9)mmol/L]比较 ,差异有显著性 (P <0 0 5 ) ,各组新生儿脐血镁离子含量比较 ,差异有极显著性 (P <0 0 1) ,对照组和治疗 2组、未治疗组和治疗 1组比较 ,差异无显著性 (P >0 0 5 ) ,其余各组间比较 ,差异有极显著性 (P <0 0 1) ,各组胎盘重量比较 ,差异有极显著性 (P <0 0 1) ,各组新生儿体重比较 ,差异有显著性 (P <0 0 5 )。结论　镁缺乏是IUGR发生的原因之一 ,中晚期孕妇适量补充镁有预防和治疗IUGR的作用     

Study of Association of Fetal Cerebroplacental Ratio with Adverse Perinatal Outcome in Uncomplicated Term AGA Pregnancies

BackgroundThe cerebroplacental ratio (CPR) is emerging as a predictor for adverse perinatal outcome in term pregnancies. Earlier, it has shown a role in small for gestational age (SGA) pregnancies, but a proportion of appropriate for gestational age foetuses (AGA) despite of good size have impaired growth velocity and are thereby at risk of adverse outcome. CPR has implication for assessment of well being of SGA and AGA foetuses close to term.ObjectiveTo investigate the association between foetal CPR and adverse perinatal outcome in uncomplicated term AGA pregnancies.MethodsThis was a prospective observational study done in Department of Obstetric and Gynaecology, King George Medical University, Lucknow, over a period of one year. Women > 37 week singleton pregnancy with no known risk factor who had Doppler USG done within a week of delivery were included. CPR was calculated by dividing the Doppler indices of middle cerebral artery (MCA) by umbilical artery (MCA PI/UA PI). CPR < 1 was taken as abnormal. These patients were followed up till delivery to look for various perinatal outcomes. Results Out of 127 low-risk AGA pregnancies who went for USG colour Doppler scan, 117 patients who met our inclusion criteria were analysed; out of 117 patients 23(i.e. 19.65 %) were having CPR < 1 and 94 patients (i.e. 80.34%) were having CPR>1. Among 23 patients with CPR < 1, 22 (91.30%) had adverse outcome as compared to only 20.21% patients with CPR > 1, and this is found to be statistically significant (p < 0.001).ConclusionOur study found CPR measure to be a very promising tool for optimising the identification of at risk foetus in low-risk AGA pregnancies.     

小于胎龄儿追赶生长与胰岛素抵抗的研究进展

小于胎龄儿（small for gestational age,SGA）多提示存在胎儿生长受限。追赶生长是纠正生长不利因素后儿童生长发育的补偿机制,因此在大部分SGA中可以观察到追赶生长现象。大量研究认为追赶生长与生命早期发生胰岛素抵抗高度相关,但目前关于追赶生长导致胰岛素抵抗的确切机制缺乏清晰的认识,因而也缺乏针对追...     

Endocrine regulation in asymmetric intrauterine fetal growth retardation

Objective. The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother.

Materials and methods. We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA).

Results. (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers.

Conclusion. Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary–thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.     

Clinical strategies for improving the detection of fetal growth restriction

The single most important condition affecting the viable fetus is intrauterine growth retardation (IUGR). IUGR is a common condition, affecting about 10% to 15% of the general maternity population. Despite its importance and relatively high prevalence, IUGR detection is poor. This article will focus on how to improve on IUGR detection.     

宫内环境因素对新生儿胰岛素敏感性影响的研究

目的　探讨宫内环境因素对新生儿胰岛素敏感性的影响。　方法　将入选 2 80例新生儿依据孕周和出生体重分为四组 :足月适于胎龄儿组 133例 ,足月小样儿组 30例 ,早产适于胎龄儿组87例 ,早产小于胎龄儿组 30例。在生后 3d上午哺乳前进行血糖、胰岛素和血脂检测 ,并计算胰岛素与血糖的比值 ,应用SPSS 9.0软件进行统计学处理。　结果　足月小样儿组与足月适于胎龄儿组胰岛素 /血糖比值分别为 1.2 4 3± 0 .70 3和 0 .2 5 9± 0 .837,早产小于胎龄儿组与早产适于胎龄儿组胰岛素 /血糖比值分别为 1.190± 0 .6 83和 0 .4 97± 0 .0 80 ,小于胎龄儿组胰岛素 /血糖比值高于适于胎龄儿组 (P <0 .0 0 1)。足月小样儿组与足月适于胎龄儿组血甘油三酯 (单位 :mmol/L)分别为 2 .399±0 .2 2 3和 1.82 5± 0 .14 1,低密度脂蛋白胆固醇 (单位 :mmol/L)分别为 2 .0 31± 0 .14 0和 1.4 80± 0 .10 4 ,早产小于胎龄儿组与早产适于胎龄儿组血甘油三酯分别为 1.774± 0 .15 9和 1.342± 0 .0 80 ,低密度脂蛋白胆固醇分别为 1.777± 0 .110和 1.336± 0 .0 70 ,小于胎龄儿组血甘油三酯和低密度脂蛋白胆固醇高于适于胎龄儿组 (P <0 .0 0 1)。妊娠高血压综合征 (简称妊高征 )母亲的新生儿胰岛素 /血糖比值平均为 1.0 77± 0 .     

Building consensus and standards in fetal growth restriction studies

Fetal growth restriction is a pathologic condition in which the fetus fails to reach its biologically based growth potential. There is inconsistency in terminology, definition, monitoring, and management, both in clinical practice and in the existing literature. This hampers interpretation and comparison of cohorts and studies. Standardization is essential.With the lack of a golden standard, or the opportunity to come to empirical evidence, consensus procedures can help to establish standardization. Consensus procedures provide no new information but formulate an agreement (as second best in the absence of robust evidence) for clinical and/or research practice on the basis of existing data. Consensus agreements need to be updated when new evidence becomes available and can change over time.In this chapter, we address the different issues that lack uniformity in FGR studies and management. Furthermore, we discuss several consensus methods and recent consensus procedures regarding fetal growth restriction.