IGF系统与胎儿生长发育

胎儿几乎所有组织中都能合成及分泌胰岛素样生长因子。胰岛素样生长因子以自分泌和旁分泌机制与靶细胞表面特异受体结合，在局部组织发挥生理作用，加强机体同化作用。其对胎儿是必需的，在胎儿组织器官生长发育和成熟中起重要作用。母体及胎盘胰岛素样生长因子水平也影响胎儿的生长。基因重组多肽类生长因子已用于产科临床治疗一些相关病症。     

IGFs在IUGR儿生后追赶生长中的作用

胰岛素样生长因子在胎儿宫内生长迟缓儿生后追赶生长中的作用,是目前胎儿学和儿童发育学中较为重要的课题。胰岛素样生长因子作用的确切机制目前尚未完全明了,但的确存在不同胎龄间胰岛素样生长因子的水平差异,以及在胎儿宫内生长迟缓儿及生后缺乏追赶生长的胎儿宫内生长迟缓儿的血胰岛素样生长因子水平降低的。     

IGFs在IU GR儿生后追赶生长中的作用

胰岛素样生长因子在胎儿宫内生长迟缓儿生后追赶生长中的作用,是目前胎儿学和儿童发育学中较为重要的课题。胰岛素样生长因子作用的确切机制目前尚未完全明了,但的确存在不同胎龄间胰岛素样生长因子的水平差异,以及在胎儿宫内生长迟缓儿及生后缺乏追赶生长的胎儿宫内生长迟缓儿的血胰岛素样生长因子水平降低的现象。本文拟通过这些现象重点说明胰岛素样生长因子在胎儿宫内生长迟缓儿生后追赶生长中的作用及与 Ｇ Ｈ 的关系。     

IGFs与胎盘发育及IUGR的相关性

胎儿宫内发育迟缓的围产期死亡率和患病率均较高，近年来内分泌与胎儿宫内发育迟缓发病机制的密切关系已被确认。胰岛素样生长因子在胎儿，胎盘的生长发育中起重要作用，妊娠过程中胎盘是母体与胎儿之间联系的枢纽，尽管对内分泌影响胎盘的中间作用环节知之甚少，但母体及胎儿胰岛素样生长因子能够寺影响胎盘新陈代谢已被证实。     

妊娠期吸烟对胎儿生长的影响

测定30例吸烟母亲的新生儿和60例不吸烟母亲的新生儿脐带血中前清蛋白、清蛋白、甘油三酯、葡萄糖、胰岛素、胰岛素样生长因子1、胰岛素样生长因子结合蛋白3、pH值、乳酸、红细胞生成素和血红蛋白浓度。结果显示,吸烟母亲的婴儿出生时体重、身长和头围均明显低于对照组,胰岛素、胰岛素样生长因子1、胰岛素样生长因子结合蛋白3浓度也明显低于对照组,血红蛋白和红细胞生成素显著高于对照组,血pH值和乳酸浓度无差别,前清蛋白、清蛋白、甘油三酯和葡萄糖浓度无明显差异。妊娠期吸烟导致胎儿匀称的生长减慢,可能是由于输送给胎儿的氧减少,胎儿的胰岛素、胰岛素样生长因子1和胰岛素样生长因子结合蛋白3浓度降低所致。     

IGFs与胎盘发育及IUGR的相关性

胎儿宫内发育迟缓的围产期死亡率和患病率均较高，近年来内分泌与胎儿宫内发育迟缓发病机制的密切关系已被确认。胰岛素样生长因子在胎儿、胎盘的生长发育中起重要作用，妊娠过程中胎盘是母体与胎儿之间联系的枢纽，尽管对内分泌影响胎盘的中间作用环节知之甚少，但母体及胎儿胰岛素样生长因子能够显著地影响胎盘新陈代谢已被证实。本文意在对其研究进展作简要介绍。     

胰岛素样生长因子结合蛋白与胎儿宫内发育

近年来研究证明，胰岛素样生长因子的缺乏可导致胎儿生长迟缓，而胰岛素样生长因子的生物活生受其受体及结合蛋白所控制。还有学者提出，胰岛素样生长因子结合蛋白的血清浓度与胎儿宫内生长有关。本文主要对ＩＧＦＢＰ１－３与胎儿宫内生长的关系加以综述。     

生长因子与激素对胎儿发育的影响

近年来内分泌因素在胎儿宫内发育迟缓（ＩＣＧＲ）发病中的作用越来越受到人们的重视。本文针对目前研究较多的表皮生长因子、胰岛素生长因子、甲状腺激素、生长激素等在ＩＵＧＲ发病中所起作用的研究进展予以综述。     

生长因子与激素对胎儿发育的影响

近年来内分泌因素在胎儿宫内发育迟缓（ＩＵＧＲ）发病中的作用越来越受到人们的重视。本文针对目前研究较多的在皮生长因子、胰岛素样生长因子、甲状腺激素、生长激素等在ＩＵＧＲ发病中所起作用的研究进展予以综述。     

胎儿生长受限与胰岛素样生长因子及其结合蛋白关系的研究

目的探讨胎儿生长受限(FGR)与胰岛素样生长因子(IGF)和胰岛素样生长因子结合蛋白(IGFBP)的关系,为FGR的临床诊断和治疗提供理论依据和新思路。方法分别采集确诊FGR组和正常对照组孕妇羊水、静脉血和胎儿脐血标本,采用放射免疫方法测定标本中IGF-Ⅰ、IGF-Ⅱ、IGFBP-3含量。结果与对照组比较,FGR组IGF-Ⅰ、IGF-Ⅱ含量在脐血、母血以及羊水标本中均明显下降,差异具有统计学意义(P<0.001),IGFBP-3含量在脐血和羊水中明显上升,差异有统计学意义(P<0.001),但在母血中无明显差异(P>0.05)。结论IGF-Ⅰ、IGF-Ⅱ和IGFBP-3参与FGR的发生和发展,测定其含量可以作为诊断FGR的指标之一。     

胎盘中的胰岛素样生长因子系统

该文详细阐述了胰岛素样生长因子系统各个成员的结构及其在胎盘中的表达和作用机制。胰岛素样生长因子系统与其受体结合 ,共同刺激胎盘滋养层细胞中类固醇激素的产生 ,与其它细胞因子协同作用 ,促进生长发育和细胞分化 ,使细胞从Gi期进入DNA合成的S期 ,能够介导和扩大生长素调节、孕激素对胎盘的功能。胰岛素样生长因子系统与胰岛素样生长因子结合蛋白发生高亲和性结合 ,后者可以通过调节胰岛素样生长因子与受体的结合影响其生物功能。深入的研究这一途径 ,对于进一步了解胎盘滋养细胞的生长发育、分化、增殖和功能之间的内在机制有重要意义。     

遗传与环境因素在胎儿生长受限发病中的作用

胎儿生长受限是围生期的重要并发症 ,居围产儿死亡原因第二位 ,远期也影响儿童期及青春期的体能与智能发育。国内外多项研究表明 ,在早孕期间 ,胎儿生长受限主要由遗传因素或基因异常引起 ,而到中孕、晚孕期间 ,由胎儿外来因素造成 ,其中包括各种环境因素。该文就遗传与各种环境因素包括化学因素、物理因素、生物因素、生活习性、营养、地理因素等对胎儿生长的影响作一综述。     

孕妇血清微量、常量元素含量及其与胎儿宫内生长迟缓关系探讨

于孕晚期测定了９７名胎儿宫内生长迟缓（ＩＵＧＲ）孕妇及１３３名正常胎儿孕妇血清中１５种微量元素及４种常量元素水平，并用多元逐步回归方法探讨了这些元素水平与胎儿生长发育的关系，结果发现：（１）ＩＵＧＲ孕妇血清Ｎａ、Ｐ、Ｃｕ、Ｍｎ、Ｍｏ、Ｖ、Ｃｒ、Ａｌ浓度显著低于对照组，而血清Ｆｅ、Ｂ浓度显著高于对照组（Ｐ＜０．０５或ｐ＜０．０１）。（２）多元回归分析结果表明，血清Ｎａ、Ｚｎ、Ｆｅ等与胎儿生长发育密切相关；孕期高硼可能对胎儿生长不利。文章讨论了孕期某些微量元素与胎儿生长发育的关系。     

The predictive ability of conditional fetal growth percentiles

Hutcheon JA, Egeland GM, Morin L, Meltzer SJ, Jacobsen G, Platt RW. The predictive ability of conditional fetal growth percentiles. Paediatric and Perinatal Epidemiology 2010; 24: 131–139. Conditional fetal growth percentiles are percentiles that are calculated taking into account (conditional on) an infant's weight earlier in pregnancy. Although they have been proposed in the statistical literature as a more methodologically appropriate method of measuring fetal growth, their ability to predict adverse perinatal outcomes due to fetal growth restriction is unknown. Using a large, unselected clinical ultrasound database at the Royal Victoria Hospital in Montreal, Canada, we calculated conditional growth percentiles for infants' weight at birth, given their weight at the time of a routine 32‐ or 33‐week ultrasound. The risk of adverse perinatal outcome (perinatal mortality, low Apgar, acidaemia, or seizures/organ failure due to asphyxia) among small‐for‐gestational‐age infants (SGA) as established by conditional growth percentiles was calculated as well as the risk among infants classified as SGA by conventional weight‐for‐gestational‐age percentiles. Regardless of the threshold used to define SGA (fifth, 10th, 15th, 20th), conditional percentiles did not appear to improve the identification of adverse perinatal outcomes compared with conventional weight‐for‐gestational‐age charts. Further work is needed to confirm our results as well as to explore potential reasons for the lack of benefits from using a measure of growth instead of size to identify fetal growth restriction.     

Gestational Diabetes Mellitus: Predictive Value of Fetal Growth Measurements by Ultrasonography at 22–24 Weeks: A Retrospective Cohort Study of Medical Records

Early intervention of gestational diabetes mellitus (GDM) is effective in reducing pregnancy disorders. Fetal growth, measured by routine ultrasound scan a few weeks earlier before GDM diagnosis, might be useful to identify women at high risk of GDM. In the study, generalized estimating equations were applied to examine the associations between ultrasonic indicators of abnormal fetal growth at 22–24 weeks and the risk of subsequent GDM diagnosis. Of 44,179 deliveries, 8324 (18.8%) were diagnosed with GDM between 24 and 28 weeks. At 22–24 weeks, fetal head circumference (HC) < 10th, fetal femur length (FL) < 10th, and estimated fetal weight (EFW) < 10th percentile were associated with 13% to 17% increased risks of maternal GDM diagnosis. Small fetal size appeared to be especially predictive of GDM among women who were parous. Fetal growth in the highest decile of abdominal circumference (AC), HC, FL and EFW was not associated with risk of subsequent GDM. The observed mean difference in fetal size across gestation by GDM was small; there was less than 1 mm difference for AC, HC, and FL, and less than 5 g for EFW before 24 weeks. Despite similar mean fetal growth among women who were and were not later diagnosed with GDM, mothers with fetuses in the lowest decile of HC, FL and EFW at 22–24 weeks tended to have higher risk of GDM.     

Fetal growth and neonatal mortality in Korea

The fetal growth curve and neonatal mortality rate, based on gestational age and birthweight, are important for identifying groups of high-risk neonates and developing appropriate medical services and health-care programmes. The purpose of this study was to develop a national fetal growth curve for neonates in Korea, and examine the Korean national references for fetal growth and death according to their characteristics. Data of Korean vital statistics linked National Infant Mortality Survey conducted on births in 1999 were used in this study. The total livebirths were 621,764 in 1999, which were grouped into singletons (n = 609,643) and twins (n = 9805) for analysis. Birthweight/gestational age-specific fetal growth curves and neonatal mortality rates were based on 250 g of birthweight and weekly gestational age intervals for each characteristic of the birth. The features of high-risk neonates such as small-for-gestational-age and the limit of viability in Korea were different from those of Western countries. Difference in fetal growth and death was also detected in other characteristics of the fetus (gender and plurality of birth) besides race. The fetal growth curve of males was higher than that of females, and was higher in singleton than in twins. The neonatal mortality rate was higher in males (singleton, 2.6; twin, 23.5) than females (singleton, 2.1; twin, 15.9), and higher in twins (19.8/1000) than in singletons (2.4/1000). However, in neonates with gestational age >29 weeks and birthweight >1000 g, the neonatal mortality rate was lower in twins than in singletons. The limit of viability was gestational age 27 weeks and birthweight 1000 g, which was similar in singletons and twins regardless of gender. To improve the health of neonates in a country, it is imperative to investigate the characteristics of fetal growth and death under the particular circumstances of the country. When risk is defined for neonates account must be taken of differences in race, gender and plurality of birth, as the neonatal mortality rate varies depending on those factors.     

早期运动干预对胎儿生长受限儿的疗效观察

目的 研究早期运动疗法对胎儿生长受限儿(FGR)智能及运动发育的影响,为促进儿童保健管理和康复治疗提供依据。方法 收集2012年7月-2013年7月FGR将240例随机分为干预组与未干预组,并设120例正常儿为对照组,对干预组实施运动干预为主,配合药物治疗、物理电治疗、音乐疗法,定期体检及智能发育测试。结果 1)干预组智能发育指数(MDI)及运动发育指数(PDI)明显高于未干预组,差异有统计学意义(P<0.001)。2)干预组经过干预治疗后遗症明显少于未干预组。3)干预组患儿在2岁时可达正常组水平,与正常组比较差异无统计学意义(P>0.05)。结论 早期运动干预可促使FGR的智能发育,提高生活质量,减少社会负担。     

Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses.     

Maternal Diet Influences Fetal Growth but Not Fetal Kidney Volume in an Australian Indigenous Pregnancy Cohort

Suboptimal nutrition during pregnancy is recognised as a significant modifiable determinant in the development of chronic disease in offspring in later life. The current study aimed: (i) to assess the dietary intakes of pregnant Indigenous Australian women against national recommendations and (ii) to investigate the associations between maternal nutrition during pregnancy and the growth of the offspring, including kidney development in late gestation in the Gomeroi gaaynggal cohort (n = 103). Maternal dietary intake in the third trimester was assessed using the Australian Eating Survey Food Frequency Questionnaire. Estimated fetal weight (EFW) and kidney size were obtained by ultrasound. Birth weight was retrieved from hospital birth records. Of the five key nutrients for optimal reproductive health (folate, iron, calcium, zinc and fibre), the nutrients with the highest percentage of pregnant women achieving the nutrient reference values (NRVs) were zinc (75.7%) and folate (57.3%), whereas iron was the lowest. Only four people achieved all NRVs (folate, iron, calcium, zinc and fibre) important in pregnancy. Sodium and saturated fat intake exceeded recommended levels and diet quality was low, with a median score of 28 out of 73 points. After adjusting for smoking and pre-pregnancy body mass index, only maternal intake of retinol equivalents and the proportion of energy from nutrient-dense or energy-dense, nutrient-poor (EDNP) foods were associated with fetal growth. EFW decreased by 0.13 g and birth weight decreased by 0.24 g for every µg increase in maternal dietary retinol intake. Interestingly, EFW, but not actual birth weight, was positively associated with percentage energy from nutrient dense foods and negatively associated with percentage energy from EDNP foods. Dietary supplement usage was associated with increased birthweight, most significantly iron and folate supplementation. Current dietary intakes of pregnant Australian women from this cohort do not align with national guidelines. Furthermore, current findings show that maternal retinol intake and diet composition during pregnancy can influence fetal growth, but not fetal kidney growth in late gestation. Strategies that aim to support and optimise nutrient intakes of Indigenous pregnant women are urgently needed. Future studies with long-term follow-up of the children in the current cohort to assess renal damage and blood pressure are imperative.     

Manganese and birth outcome

Manganese is an essential mineral nutrient needed for proper fetal development and other important aspects of metabolism. However, manganese excess can have a potent neurotoxicity effect, especially in infants. Little is known about the effects of manganese deficiency or excess on the developing human fetus. The findings of two recent studies indicate that lower maternal blood manganese is associated with fetal intrauterine growth retardation (IUGR) and lower birth weight. In light of the importance of IUGR and birth weight on neonatal morbidity and mortality, additional basic studies of maternal and fetal manganese physiology are needed, as well as more epidemiologic studies in different populations of the association of manganese exposure and birth outcome.