胰岛素样生长因子及胰岛素样生长因子结合蛋白-3与胎儿生长受限的关系

目的　探讨胰岛素样生长因子 (IGF) Ⅰ、IGF Ⅱ和IGF结合蛋白 3(IGFBP 3)与胎儿生长的关系 ,以及IGF在胎儿生长受限 (FGR)发病中的作用。方法　选取 2 0例分娩FGR胎儿 (FGR组 )、10例分娩巨大儿 (巨大儿组 )及 2 0例分娩正常儿 (对照组 )的产妇 ,抽取 3组产妇分娩后肘静脉血及其新生儿脐静脉血 ,分离血清。采用放射免疫法和免疫放射法测定 3组产妇及其新生儿血清中IGF Ⅰ、IGF Ⅱ及IGFBP 3的水平。结果　 (1)FGR组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为(130 5± 2 6 0 ) μg/L、(2 40± 0 42 ) μg/L及(5 5 79± 848) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 6± 1 7) μg/L、(1 5 4± 0 31) μg/L及 (86 9± 183) μg/L。 (2 )巨大儿组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 9 7± 44 6 ) μg/L、(2 43± 0 2 5 ) μg/L及(5 5 6 2± 742 ) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 9 6± 2 3 9) μg/L、(2 19± 0 2 9) μg/L及(16 82± 130 )μg/L。(3)对照组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 7 9± 70 7) μg/L、(2 41± 0 36 )μg/L及 (5 5 86± 6 78) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 8 9     

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks in trisomy 21 and trisomy 18 pregnancies

Objective

To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 in first-trimester screening for fetal aneuploidies.

Study design

Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation were measured and compared in 30 trisomy 21, 30 trisomy 18 and 120 euploid pregnancies.

Results

The median multiple of the normal median (MoM) values of maternal serum IGF-I, IGFBP-1 and IGFBP-3 in trisomy 21, trisomy 18 and euploid pregnancies were not significantly different (IGF-I: 1.10, 1.14 and 1.0 MoM, respectively; IGFBP-1: 1.10, 1.01 and 1.0 MoM; IGFBP-3: 0.90, 1.16 and 0.98 MoM).

Conclusion

Measurement of maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation is unlikely to be useful in screening for trisomies 21 and 18.     

Does the physiological acromegaly of pregnancy benefit the fetus?

Pregnancy is accompanied by notable changes in the secretion of growth hormone (GH) and the insulin-like growth factors (IGFs). A GH variant produced by the placenta is discernible in maternal plasma from early pregnancy, rising exponentially until 37 weeks. Meanwhile, pituitary GH gradually drops to near-undetectable levels. While there might be a modest reduction in circulating IGF-I in early pregnancy, IGF-I increases 2- to 3-fold in the second half, again with a peak at around 37 weeks. Thus, placental GH is believed to replace pituitary GH as the primary stimulus for IGF-I secretion in pregnancy. Several IGF-binding proteins (IGFBPs) including IGFBP-3 are proteolyzed, leading to an elevated free (bioavailable) IGF-I fraction. IGF-II concentrations also appear to show a modest (20-25%) increase in the course of pregnancy. The possible clinical manifestations include edema of face and forearms and carpal tunnel symptoms, reminiscent of the symptoms of acromegaly and the side effects of GH/IGF-I treatment. Neither placental GH nor the maternal IGFs cross the placental barrier, yet evidence from preclinical models is accumulating that they promote trophoblast invasion, placenta growth and maturation, transplacental nutrient transport and, ultimately, fetal growth. The ensemble data strongly suggest that 'gestational acromegaly' develops in order to foster fetoplacental growth.     

IGF-1、IGF-2、IGFBP-3与非糖尿病孕妇巨大儿发生的相关性研究

目的探讨胰岛素样生长因子1、2（IGF-1、IGF-2）、胰岛素样生长因子结合蛋白3（IGFBP-3）与非糖尿病孕妇巨大儿发生的关联性。方法选择2010年1月至2011年5月于上海市浦东新区人民医院产前检查并分娩的初产妇,孕期纵向观察,抽取妊娠中期（26～28周）和妊娠足月（38～41周）的母血及孕妇分娩时新生儿出生体重≥4000g30例（巨大儿组）、2500～3500g30例（正常组）的脐血,应用放射免疫法检测IGF-1、IGF-2、IGFBP-3的水平,并进行对比分析。结果①两组孕妇妊娠足月IGF-1水平均高于妊娠中期,差异有高度统计学意义（分别为P〈0.0001、P〈0.001）,但妊娠中期和足月时,巨大儿组与正常组二组间比较差异均无统计学意义（P〉0.05）。巨大儿组脐血IGF-1水平高于正常组,差异有高度统计学意义（P〈0.0001）;②孕妇血清IGF-2水平巨大儿组与正常组比较差异无统计学意义（P〉0.05）;③孕妇妊娠中期、妊娠足月血清IG-FBP-3水平巨大儿组明显高于正常组,差异有高度统计学意义（分别为P〈0.001、P〈0.01）;④母血IGFBP-3水平、脐血IGF-1水平与新生儿出生体重正相关。结论 IGF-1参与了胎儿生长发育的调节;胎儿自身循环中的IGF-1与新生儿出生体重有关;非糖尿病孕妇血清IGFBP-3水平与巨大儿形成有关。     

Circulating insulin-like growth factor (IGF)-I and IGF binding proteins -1 and -3 and placental development in the guinea-pig

Restricting maternal nutrition before and throughout pregnancy in the guinea-pig restricts foetal growth in part by altering placental structural determinants of substrate transfer function. The insulin-like growth factors have been implicated in mediating these changes. To assess the role of IGF-I in placental adaptation to maternal undernutrition, we examined the associations of circulating IGF-I and IGF binding proteins -1, -3 and -4 in the mother with placental structural development. In both mid- and late pregnancy, maternal food restriction reduced maternal plasma IGF-I by 56 per cent (P<0.0005) and 50 per cent (P<0.0005) respectively, and plasma IGFBP-3 by 47 per cent (P=0.03) and 55 per cent (P=0.002), respectively. Maternal plasma IGFBP-4 was reduced by 45 per cent (P=0.041) in food restricted guinea-pigs in mid-pregnancy but not late in pregnancy, while IGFBP-1 was unaltered at both stages. Late in pregnancy, food restriction reduced the ratio of maternal circulating IGF-I to IGFBP-1 by 52 per cent (P=0.011) and increased the ratio of IGF-I to IGFBP-3 in maternal plasma by 10 per cent (P=0.011). The relationships between the maternal IGF axis and structural correlates of placental function were assessed using pooled data from both ad libitum fed and food restricted animals. In mid-pregnancy, the volume density of the maternal blood space in the placental labyrinth correlated positively with both maternal plasma IGF-I and IGFBP-3, while maternal blood space volume correlated negatively with maternal plasma IGFBP-1. In late pregnancy, placental weight correlated positively with both maternal plasma IGF-I and IGFBP-4, while the surface area of syncytiotrophoblast and weight of trophoblast correlated positively, and mean syncytiotrophoblast thickness negatively, with maternal plasma IGF-I. Late in pregnancy, the volume density and weight of syncytiotrophoblast, the surface density and total surface area of trophoblast and the volume of the maternal blood space each correlated positively, and syncytiotrophoblast thickness correlated negatively with maternal plasma IGFBP-3. Concomitantly, placental weight, placental diameter, placental volume, volume density and weight of syncytiotrophoblast, weight of foetal capillaries, syncytiotrophoblast surface density and total syncytiotrophoblast surface area in the placental labyrinth, each correlated positively with the ratio of IGF-I to IGFBP-1 in maternal plasma, while syncytiotrophoblast thickness correlated negatively with this ratio. In late pregnancy therefore, increased trophoblast abundance and placental vascularity, and a reduced barrier to diffusion between maternal and foetal blood, occurs in association with increased abundance of IGF-I and its major carrier, IGFBP-3, and a reduction in that of IGFBP-1 in maternal blood in the guinea-pig. This suggests that systemic IGF-I and modulation of its bioavailability by IGFBPs -1 and -3 within the mother may influence placental growth and differentiation in an endocrine fashion, particularly when nutrition is limited.     

Insulin-like growth factor 1 and its binding protein 1 during normal and diabetic pregnancies.

Investigations of circulating insulin-like growth factor 1, hPL, and infant size during pregnancy in normal and insulin-dependent diabetic women have yielded conflicting results and have not been analyzed longitudinally. We studied serial changes in maternal serum insulin-like growth factor 1 levels (measured by radioimmunoassay after acid ethanol extraction) throughout pregnancy in 22 normal women and in 38 with insulin-dependent diabetes. The diabetic women had significantly lower serum insulin-like growth factor 1 concentrations than normal women throughout pregnancy and after delivery, although the rates of change in both groups of women were similar. Within-patient analysis showed a significant decrease in serum insulin-like growth factor 1 between 6-12 weeks' gestation and a significant increase between 24-32 weeks, followed by a significant decrease from 36 weeks' gestation to 12 weeks after delivery. Incremental changes in insulin-like growth factor 1 between 24-32 weeks' gestation correlated significantly with incremental changes in hPL (r = 0.40; P less than .001) and with birth weight (r = 0.37; P less than .01), but not with ultrasound measurements of fetal growth. The correlation of increments in insulin-like growth factor 1 and birth weight became nonsignificant when the association of hPL with both insulin-like growth factor 1 and birth weight was taken into account. Neither insulin-like growth factor binding protein 1 (placental protein 12) nor its ratio to insulin-like growth factor 1 showed any association with infant size. The physiologic changes in maternal serum insulin-like growth factor 1 in pregnant diabetic women do not appear related to the increased birth weight of their infants.     

The IGF axis in baboon pregnancy: placental and systemic responses to feeding 70% global ad libitum diet

Information on the influence of poor maternal nutrition on the regulation of responses to pregnancy, placental and fetal growth and development is critical to a better understanding of pregnancy physiology and pathophysiology. We determined normal changes and effects of controlled and monitored moderate nutrient restriction (NR) (global nutrient intake reduced to 70% of food consumed by mothers feeding ad libitum from 0.16 to 0.5 of gestation) in the baboon, on important hematological, biochemical, and hormonal indices of fetal growth and placental function. Serum IGF-I:IGFBP-3 ratio was lower in pregnant than control non-pregnant baboons feeding ad libitum. Serum concentrations of total and free IGF-I were decreased in NR mothers compared with controls (p<0.05). The decrease in fetal IGF-I did not reach significance (p=0.057). Serum IGF-I: IGFBP-3 ratio was decreased by NR in both mothers and fetuses. Maternal serum IGF-II was unchanged by NR. Placental IGF-I mRNA and protein abundance were similarly reduced whereas IGF-II mRNA increased in placental tissue of NR compared to control mothers. Systemic (maternal) and local (placental) IGFBP-1 and IGFBP-3 mRNA and protein abundance were unchanged by NR. Type 1 IGF receptor protein in the syncytiotrophoblast increased in NR. Type 2 IGF receptor protein was present in the stem villi core, and decreased after NR. We conclude that moderate NR in this important non-human primate model significantly disrupts the maternal and placental IGF-IGFBP axis and influences placental expression of this key system at the gene and protein level. Changes observed appear to be directed toward preserving placental growth.     

Maternal interleukin-6: marker of fetal growth and adiposity

Fetal overgrowth and higher adiposity are hallmarks of pregnancy with maternal obesity and poor glucose tolerance, two conditions associated with decreased maternal insulin sensitivity. In non-pregnant individuals, adipokines, vasoactive peptides, and components of the immune system crosstalk with metabolic factors to generate signals triggering obesity and impaired insulin action. We have investigated circulating maternal and fetal cytokines and growth-factors as potential biochemical markers of fetal adiposity. Mothers and neonates were classified into three tertiles (T1-T3) using total neonatal fat mass as the outcome with 309 +/- 25 g in T1, 478 +/- 40 g in T2, and 529 +/- 39 g in T3. Umbilical cord endothelin-1 (ET-1), C-peptide, and leptin were higher in T3 and T2 versus T1. Only cord leptin was strongly associated with fetal fat mass (P < .01), whereas neonatal lean body mass was negatively correlated with maternal insulin-like growth factor binding protein-I (IGFBP-I) (r = -0.53, P < .04). This study shows an association between increased fetal adiposity and maternal systemic interleukin-6 (IL-6). No such correlation was found with factors circulating in cord blood, suggesting that the stimuli favoring fetal fat accretion derive from maternal or placental sources rather than from the fetus.     

Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11-13 weeks' gestation in pregnancies delivering small for gestational age neonates

Objective

To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 at 11–13 weeks’ gestation in the prediction of small-for-gestational age (SGA) neonates.

Study design

Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks were measured in 60 cases that subsequently delivered SGA neonates in the absence of pre-eclampsia, and compared to 120 non-SGA controls.

Results

In the SGA group, compared to the non-SGA group, there was significantly lower median IGF-I (61.8, IQR 43.4–93.4 ng/mL vs 94.9, IQR 56.7–131.2 ng/mL, p = 0.002) and IGFBP-1 (58.2, IGR 39.8–84.9 ng/mL vs 81.4, IGR 57.3–105.5 ng/mL, p = 0.002) but not IGFBP-3 (54.5, IGR 45.6–61.5 ng/mL vs 55.4, IGR 47.4–64.9 ng/mL, p = 0.402). However, after multiple regression analysis and adjustment for maternal characteristics, these biomarkers were not useful in predicting SGA.

Conclusion

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks are unlikely to be useful biochemical markers for early prediction of SGA.     

Beginning regular exercise in early pregnancy: effect on fetoplacental growth

OBJECTIVE: Our purpose was to test the null hypothesis that beginning regular, moderate-intensity exercise in early pregnancy has no effect on fetoplacental growth.Study Design: Forty-six women who did not exercise regularly were randomly assigned at 8 weeks either to no exercise (n = 24) or to weight-bearing exercise (n = 22) 3 to 5 times a week for the remainder of pregnancy. Outcome variables included antenatal placental growth rate and neonatal and placental morphometric measurements. RESULTS: The offspring of the exercising women were significantly heavier (corrected birth weight: 3.75 +/- 0.08 kg vs 3.49 +/- 0.07 kg) and longer (51.8 +/- 0.3 cm vs 50.6 +/- 0.3 cm) than those born to control women. The difference in birth weight was the result of an increase in both lean body mass and fat mass. In addition, midtrimester placental growth rate was faster (26 +/- 2 cm(3)/wk vs 21 +/- 1 cm(3)/wk) and morphometric indexes of placental function were greater in the exercise group. There were no significant differences in neonatal percentage body fat, head circumference, ponderal index, or maternal weight gain. CONCLUSIONS: These data indicate that beginning a moderate regimen of weight-bearing exercise in early pregnancy enhances fetoplacental growth.     

Pregnancy-induced changes in insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) in patients with growth hormone (GH) deficiency and excess

BACKGROUND: Under most circumstances with altered growth hormone (GH) secretion, the changes of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) are in parallel. The aim of the present study was to compare the effects of pregnancy in a hypopituitary patient with those of pregnancy in an acromegalic patient on IGF-I, IGFBP-3, and ALS. METHODS AND RESULTS: IGF-I and ALS were low before pregnancy in the hypopituitary patient under glucocorticoid and thyroxine treatment. Gonadotropin treatment allowed her to become pregnant; IGF-I and ALS levels rose in the second half of pregnancy and fell again after delivery. IGF-I concentrations were elevated in the patient with persistent acromegaly before and dropped into the normal range during the first half of pregnancy. In the second half of pregnancy and following delivery, IGF-I levels increased again. IGFBP-3 levels (as assessed by immunoblot analysis as well as by 125I-IGF II ligand blotting) decreased markedly during pregnancy in both patients, suggesting that the placenta rather than pituitary GH regulates IGFBP-3 proteolysis in human pregnancy. The increase of IGF-I (and ALS) during the second half of pregnancy in the individual with pituitary GH deficiency may be attributed to placental GH. The fall of IGF-I (and ALS) into the normal range in the acromegalic patient during the first trimester of pregnancy may be related to decreased production or decreased half-life of these proteins. CONCLUSION: Our data suggest that measures to continuously replace GH or to suppress GH secretion during pregnancy in patients with GH deficiency or excess, respectively, may not be warranted.     

Maternal serum insulin-like growth factor binding protein-1 in pregnancy at high altitude

OBJECTIVE: To investigate the effect of environmental hypoxia at 4300-m altitude on the maternal serum concentration of insulin-like growth factor binding protein-1 (IGFBP-1). METHODS: We conducted a cross-sectional study of 108 pregnant women in Peru, 62 from high altitude (4300 m, 14100 ft) and 46 from sea level at 14-42 weeks' gestation. For comparison, 20 healthy nonpregnant women (ten from high altitude and ten from sea level) were also examined. Total and nonphosphorylated IGFBP-1 were measured in maternal serum. RESULTS: Both total and nonphosphorylated IGFBP-1 were higher at high altitude than at sea level in the pregnant groups (ratio = 1.28, P =.008, and ratio = 1.45, P =.003, respectively), and there was significant interaction between high altitude and sea level (P =.037 and P =.043, respectively). The threshold model showed that the difference became significant from 25 weeks' gestation onwards. CONCLUSION: Before 25 weeks of pregnancy, there was no significant difference in IGFBP-1 between women living at high or low altitude, suggesting that the increased IGFBP-1 at high altitude is unlikely to be related to inadequate trophoblast invasion resulting in placental hypoxia. In the second half of pregnancy, the maternal and fetal demands increase dramatically, and low atmospheric oxygen with resulting maternal systemic hypoxemic hypoxia may cause placental hypoxia. This stimulates increased production of IGFBP-1, which in turn restricts the insulin-like growth factor-mediated fetal growth as an adaptive mechanism to prevent worsening of the fetoplacental hypoxia.     

妊娠期肝内胆汁淤积症患者血清中miR-21和IGFBP-3的表达及与围生儿结局的关系

目的:探讨妊娠期肝内胆汁淤积症(ICP)患者血清中微小RNA-21(miR-21)和胰岛素样生长因子结合蛋白3(IGFBP-3)的表达及两者与围生儿结局的关系。方法:选取四川省妇幼保健院收治的62例ICP患者作为研究组,同期健康体检孕妇62例为对照组,收集产前静脉血,采用实时荧光定量聚合酶链反应(qRT-PCR)检测血清中miR-21和IGFBP-3的相对表达量,比较两者相关性及与围生儿结局的关系。结果:研究组孕妇血清miR-21表达水平高于对照组,IGFBP-3表达水平低于对照组,差异有统计学意义(均P<0.05)。ICP患者血清中miR-21表达水平与IGFBP-3表达水平呈负相关(r=-0.783,P=0.000)。miR-21高表达组患者早产、剖宫产、羊水粪染发生率均高于miR-21低表达组,分娩孕周和新生儿出生体质量低于miR-21低表达组,差异有统计学意义(均P<0.05)。2组新生儿窒息和胎死宫内发生率比较,差异无统计学意义(均P>0.05)。IGFBP-3低表达组患者早产、剖宫产、羊水粪染发生率均高于IGFBP-3高表达组,分娩孕周和新生儿出生体质量低于IGFBP-3高表达组,差异有统计学意义(均P<0.05)。2组新生儿窒息和胎死宫内发生率比较,差异无统计学意义(均P>0.05)。结论:ICP患者血清中miR-21表达升高,IGFBP-3表达降低,二者呈负相关,miR-21高表达和IGFBP-3低表达患者围生儿不良结局发生率高,临床中应加以重视。     

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     

Maternal zinc and cord blood zinc, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels in small-for-gestational-age newborns

PURPOSE: To determine the relationship between maternal serum zinc (Zn) levels and birth weight of the offspring and their correlation with cord blood Zn, insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels. METHOD: 22 term small-for-gestational-age (SGA) and 34 term appropriate-for-gestational-age (AGA) infants and their mothers were included. Maternal and cord blood Zn levels and cord blood IGF-1 and IGFBP-3 levels were measured. RESULTS: Eighteen percent of mothers had Zn deficiency (< 75 mcg/dl). No significant difference between IGF-1 and IGFBP-3 levels and birth weight of infants of the mothers with and without Zn deficiency was found. Maternal and neonatal Zn levels correlated (r = 0.38, p < 0.01). Mean IGF-1 and IGFBP-3 levels were significantly lower in the SGA group compared to the AGA group (42.3 +/- 16.8 ng/ml, 1.2 +/- 0.2 mcg/ml, and 62.4 +/- 22.7 ng/ml, 1.5 +/- 0.4 mcg/ml, p < 0.001). A correlation was found between birth weight, IGF-1 and IGFBP-3 levels, and weight gain of the mother during pregnancy (p < 0.01). CONCLUSIONS: Zn deficiency was not observed to be a risk factor for low birth weight. The significant difference between the SGA and AGA babies' IGF-1 and IGFBP-3 levels emphasizes function of the IGF system in intrauterine growth.     

Placental alkaline phosphatase de-phosphorylates insulin-like growth factor (IGF)-binding protein-1

Background

Insulin-like growth factors (IGF) regulate fetal growth through their effects on placenta. Their actions are influenced by IGF binding protein-1. Phosphorylated IGFBP-1 (pIGFBP-1) has high affinity for IGF-I and usually inhibits IGF-I activity but during pregnancy, it is de-phosphorylated to generate lower affinity isoforms and consequently, increased IGF bioavailability. Here we investigate the role of placenta in this process.

Results

Our data show that term human placental explants, but not their conditioned medium, can de-phosphorylate IGFBP-1 through the action of placental alkaline phosphatase (PLAP).

Discussion

PLAP-mediated de-phosphorylation of IGFBP-1 may provide a mechanism for controlling IGF-I bioavailability and action at the maternal/fetal interface.     

Relationship of insulin-like growth factor-I and insulin-like growth factor binding proteins in umbilical cord plasma to preeclampsia and infant birth weight.

OBJECTIVE: To determine whether preeclampsia influences insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor binding protein-3 (IGFBP-3), independent of its effect on birth weight. METHODS: Cord blood was collected in 12,804 consecutive deliveries. We identified 258 preeclamptic pregnancies that were subclassified as mild or severe and early or late. For comparison, 609 control pregnancies were selected. Fetal growth was expressed as the ratio between observed and expected birth weight, with adjustment for gestational age at birth. IGF-I, IGFBP-1, and IGFBP-3 were measured in umbilical plasma. The contribution of preeclampsia and birth weight to each measured factor was assessed by multiple linear regression analyses. RESULTS: Between mild preeclampsia and controls, there were no differences in IGF-I, IGFBP-1, and IGFBP-3. In severe and early onset preeclampsia, umbilical cord plasma IGF-I was approximately 50% lower, and IGFBP-1 was more than twice as high as in controls (both P <.01). At each birth weight level, IGF-I was lower and IGFBP-1 was higher in severe or early preeclampsia than among controls of similar weight. Birth weight and preeclampsia were, independent of each other, associated with IGF-I, whereas birth weight, but not preeclampsia, was associated with IGFBP-1, after adjustment for gestational age. CONCLUSION: Fetal growth restriction caused by severe or early preeclampsia is associated with lower umbilical levels of IGF-I than low birth weight caused by other conditions. Preeclampsia may contribute to the observed IGF-I reduction, either as part of the underlying causes of preeclampsia, or as a consequence of the disease.     

An immunohistochemical study of type I insulin-like growth factor receptors in the placentae of pregnancies with appropriately grown or growth restricted fetuses.

Insulin-like growth factors (IGFs) and their receptors in the fetus are essential for growth and postnatal survival but the role of maternal IGFs is less well understood. Animal and in vitro evidence suggests that maternal IGF-I may have important effects on placental function. Recent work in humans suggests that although there is no relationship between maternal serum IGF-I and normal fetal growth, levels are low in pregnancies complicated by fetal growth restriction due to placental dysfunction. A prospective and observational study was undertaken of the distribution and concentration of placental type I IGF receptors (IGF-IR) in women with small for gestational age (n=26) or appropriately grown (n=14) fetuses. Women were scanned biweekly from 24 weeks to delivery and cases (birthweight <5th centile) were assigned to two groups: 'fetal growth restriction' (FGR; umbilical artery pulsatility index [UAPI] > +2 s.d.; n=16) and 'normal small for gestational age' (SGA; normal UAPI, growth velocity and amniotic fluid; n=10). Immunohistochemistry of the IGF-IR was performed on formol saline-fixed placental biopsies obtained at delivery. In control pregnancies IGF-IR were present in villous endothelium and stroma, trophoblast and decidua and their distribution and density were unchanged in both SGA and FGR pregnancies. We hypothesize that a therapeutic elevation of maternal IGF-I in FGR pregnancy might lead to enhanced placental function and so fetal growth. Our findings of normal localization and density of placental IGF-IR in FGR encourage us to extend our work to look at the effects of maternal IGF-I on the transport of glucose and amino acids.     

The correlation between birth weight and insulin-like growth factor-binding protein-1 (IGFBP-1), kisspeptin-1 (KISS-1), and three-dimensional fetal volume

Purpose: This study aimed to determine the relationship between birth weight, and maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) and kisspeptin-1 (KISS-1) levels, and first-trimester fetal volume (FV) based on three-dimensional ultrasonography.

Materials and methods: The study included 142 pregnant women at gestational week 11°–13⁶. All fetuses were imaged ultrasonographically by the same physician. Maternal blood samples were collected at the time of ultrasonographic evaluation and analyzed for IGFBP-1 and KISS-1 levels via enzyme-linked immunosorbent assay (ELISA). Maternal and neonatal weights were recorded at birth. Birth weight ≤10th and the >90th percentiles was defined as small and large for gestational age (SGA and LGA), respectively.

Results: Median crown-rump length (CRL), FV, and maternal serum IGFBP-1 and KISS-1 levels were 58.2?mm (35.3–79.2?mm), 16.3?cm³ (3.8–34.4?cm³), 68.1?ng?mL^?1 (3.8–377.9?mL^?1), and 99.7?ng?L^?1 (42.1–965.3?ng?L^?1), respectively. First-trimester IGFBP-1 levels were significantly lower in the mothers with LGA neonates (p?p?>?.05). The maternal IGFBP-1 level during the first trimester was a significant independent factor for SGA and LGA neonates (Odds ratio (OR): 0.011, 95%CI: 1.005–1.018, p?p?=?.007, respectively). There was no significant relationship between SGA or LGA, and CRL, FV, or the KISS-1 level.

Conclusions: As compared to the maternal KISS-1 level, the maternal IGFBP-1 level during the first trimester might be a better biomarker of fetal growth. Additional larger scale studies are needed to further delineate the utility of IGFBP-1 as a marker of abnormal birth weight.     

Serum levels and molecular sizes of growth hormone during pregnancy in relation to levels of lactogens, insulin-like growth factor I and insulin-like growth factor binding protein-1.

Growth hormone (GH), placental lactogen (PL), prolactin (PRL), insulin-like growth factor I (IGF-I) and IGF binding protein-1 (IGFBP-1) were determined in serum by radioimmunoassays (RIAs) in 12 women during pregnancy. GH and PL were analyzed by two monoclonal antibodies (Mab 3 and Mab 1) raised against pituitary GH. Serum IGFBP-1 had reached maximum levels at midpregnancy while PRL, PL and IGF-I increased continuously during pregnancy. Mab 1, which cross-reacts with PL, measured consistently higher levels of PL in serum than a commercial PL RIA (p less than 0.01) due to interference of cross-reacting serum proteins in the Mab 1 RIA. The GH-specific Mab 3 showed decreasing GH levels in unfractionated serum throughout gestation, but detected GH-immunoreactive proteins of approximately 40-200 kD after molecular sieve chromatography of pooled serum from late pregnancy. It is suggested that the formation of GH complexes of large molecular mass account for the successive disappearance of monomeric GH during pregnancy.