The relationship among intrauterine growth, insulinlike growth factor I (IGF-I), IGF-binding protein-3, and bone mineral status in newborn infants

Insulinlike growth factors (IGFs) exert profound effects on somatic growth and cellular proliferation of many tissues and play an essential role in bone metabolism. The aim of this study was to investigate how fetal growth and bone mineralization correlate with IGF-I and IGF-binding protein-3 (IGFBP-3) levels of newborn infants and their mothers. In addition, we aimed to determine the predictive value of anthropometric measurements on variability in bone mineral status. Umbilical cord venous blood samples were obtained at delivery from 100 term newborn infants. Forty of the newborn infants had birthweights appropriate for gestational age (AGA), 30 were small for gestational age (SGA), and 30 were large for gestational age (LGA). Data were acquired using whole-body dual-energy X-ray absorptiometry scanner with a pediatric platform. Umbilical cord serum IGF-I concentrations were higher in LGA newborns ( P < 0.01), but lower in SGA newborns ( P < 0.01) than in AGA newborns. Umbilical cord serum IGFBP-3 concentrations in LGA newborns were significantly greater than in SGA and AGA newborns ( P < 0.01 and P < 0.01, respectively). Whole-body bone mineral density (WB BMD) was higher in LGA babies (0.442 +/- 0.025 g/cm2 [SD]; P < 0.01) but lower in SGA (0.381 +/- 0.027 g/cm 2; P < 0.0001) than in AGA babies (0.426 +/- 0.022 g/cm2). WB BMD and content (WB BMC) were correlated significantly with birthweight, birth height, head circumference, body mass index (BMI) of the infants; ponderal index and triceps skinfold thickness (reflecting fat stores) of the infants; cord serum IGF-I concentration, serum IGF-I concentration of the mothers; and fat mass, proportionate fat mass, weight, and BMI of the mothers. In contrast, WB BMC was also correlated positively with cord serum IGFBP-3 concentration and gestational age, and WB BMD was positively correlated with serum IGFBP-3 levels of the mothers. Umbilical cord serum IGF-I concentration of the infants was correlated significantly with the concentration of the mothers ( R = 0.232; P = 0.020). Umbilical cord serum IGF-I and IGFBP-3 concentrations were correlated significantly with the fat mass, gestational age, birthweight, birth height, head circumference, and BMI of the infants. Umbilical cord IGF-I concentration was also correlated with ponderal index and triceps skinfold thickness of the infants, maternal weight, BMI, and proportionate fat mass of the infants. Stepwise multiple regression analyses showed no significant relation between bone indices (WB BMD, WB BMC) and the infant's or mother's variations including serum IGF-I and IGFBP-3 concentrations. Birthweight and gestational age are related to bone indices. However, the present study does not provide support for the hypothesis that serum IGF-I and IGFBP-3 levels of infants and their mothers may play a major role in the regulation of bone metabolism in the developing skeleton.     

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     

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 and fetal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3, and their relationship to fetal acidosis at delivery

OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and in fetal cord blood at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, Illinois, USA), with p<0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking and in fetal blood by cord blood analysis at delivery. Cord pH was also recorded. RESULTS: There was no significant correlation between maternal IGF-1, IGF-2, or IGFBP-3 levels and fetal acidosis. However, a significant correlation does exist between cord IGF-1 levels and fetal acidosis. CONCLUSION: Fetal cord IGF-1 has a significant correlation with fetal acidosis at delivery.     

Transforming growth factor-beta1 in fetal serum correlates with insulin-like growth factor-I and fetal growth

OBJECTIVE: To estimate whether transforming growth factor-beta1 in fetal serum obtained by umbilical cord sampling at delivery is correlated with fetal growth. We also estimated whether transforming growth factor-beta1 is correlated with insulin-like growth factor-I and insulin-like growth factor binding protein-1, which have been shown to correlate with fetal growth. METHODS: The active form of transforming growth factor-beta1 was analyzed in serum from cord blood from 68 fetuses by the enzyme-linked immunosorbent assay technique. Of the 68 pregnant women, 12 had preeclampsia, 14 had preeclampsia and intrauterine growth restriction, 15 had intrauterine growth restriction alone, and seven had fetuses that were large for gestational age (LGA). Twenty pregnancies with fetuses appropriate for gestational age (AGA) served as controls. RESULTS: Transforming growth factor-beta1 concentrations were significantly correlated with birth weight. The average transforming growth factor-beta1 concentration in the following groups were: intrauterine growth restriction, 22.4 +/- 2.7 microg/L; intrauterine growth restriction plus preeclampsia, 22.9 +/- 2.0 microg/L; preeclampsia without intrauterine growth restriction, 28.8 +/- 2.1 microg/L; LGA, 30.3 +/- 4.3 microg/L; and AGA, 36.8 +/- 2.0 microg/L. Transforming growth factor-beta1 levels were significantly lower in pregnancies complicated by intrauterine growth restriction and showed a positive correlation with birth weight (r = 0.48, P <.001). Furthermore, there was a positive correlation between insulin-like growth factor-I levels and birth weight (r = 0.36, P <.01) and a negative correlation between insulin-like growth factor binding protein-1 and birth weight (r = -0.32, P <.01). There was also a correlation between transforming growth factor-beta1 and insulin-like growth factor-I (r = 0.29, P <.05) and between transforming growth factor-beta1 and insulin-like growth factor binding protein-1 (r = -0.25, P <.05). CONCLUSION: Transforming growth factor-beta1 might be related to fetal growth in pregnancy. The results also support previous data showing that insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to fetal growth.     

Fetal serum levels of insulin, growth hormone and insulin-like growth factor-I in concordant and discordant twin gestations

OBJECTIVE: To examine the role of insulin, growth hormone and insulin-like growth factor (IGF)-I in concordant and discordant twin pairs. METHODS: Umbilical cord serum samples were obtained from 20 twin pairs with weight discordancy (intertwin birth weight difference > 20%) and from 20 concordant twins (intertwin birth weight difference < 20%), both groups of similar gestational age, gravidity, and parity. The serum samples were analyzed for the levels of IGF-I, growth hormone and insulin in both maternal and fetal compartments. RESULTS: Among the group of discordant twins, the normally grown twin, in all cases, had significantly higher cord serum IGF-I levels than their growth-restricted co-twin (108 +/- 73 ng/ml vs. 39 +/- 24 ng/ml; p < 0.01). There were no significant intertwin differences in the cord blood IGF-I levels in the concordant twin pairs (87 +/- 44 vs. 88 +/- 48 ng/ml; p = 0.986). Insulin and growth hormone levels did not correlate with intertwin birth weight differences. CONCLUSION: These data demonstrate that IGF-I is important in the regulation of both normal and restricted fetal growth in utero, and its action appears to be, at least in part, through an endocrine action. The precise role of growth hormone and insulin in fetal growth restriction remains uncertain.     

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.     

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 insulin-like growth factor-I and insulin-like growth factor binding protein-3 in premature rupture of membranes

BACKGROUND: The aim of the study was to evaluate whether the circulating levels of insulin-like growth factor-I (IGF-I) and its major circulating binding protein, IGFBP-3, are affected in premature rupture of membranes (PROM) and preterm delivery. METHODS: The levels of IGF-I and IGFBP-3 were measured in 32 pregnant women with PROM and in 27 healthy gestational age-matched pregnant women. Statistical analyzes were performed by analysis of variance. RESULTS: All the patients with PROM had preterm delivery, at a gestational age of 31.9 +/- 0.4 weeks (mean +/- SEM). In the control subjects, pregnancy proceeded to term. In the PROM patients, the serum IGF-I and IGFBP-3 levels (289 +/- 21 ng/ml and 8248 +/- 407 ng/ml, respectively) were not statistically different from those in the control subjects (275 +/- 22 ng/ml and 7579 +/- 488 ng/ml). Seventeen patients with PROM showed a rise in serum C-reactive protein, indicating subclinical intrauterine infection. Also in this subgroup of patients the levels of serum IGF-I (281 +/- 27 ng/ml) and IGFBP-3 (9010 +/- 633 ng/ml) were not different from those in the control subjects. Before delivery, serial serum samples were available from 22 patients with PROM. No consistent changes in IGF-I or IGFBP-3 concentrations were seen during the mean follow-up period of 9 days. CONCLUSIONS: IGF-I and IGFBP-3 do not appear to play any significant role in the maintenance of pregnancy in PROM patients with preterm delivery, whether or not associated with emerging intrauterine infection.     

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。     

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.     

Plasma adrenomedullin levels in pregnancies with appropriate for gestational age and small for gestational age infants.

AIMS: To evaluate whether maternal and fetal plasma adrenomedullin levels in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. METHODS: Maternal and fetal circulating adrenomedullin levels were compared between 62 pregnancies with AGA (43 delivered vaginally and 19 delivered by elective cesarean section) and 28 pregnancies with SGA (20 delivered vaginally and 8 delivered by elective cesarean section) at birth. Plasma adrenomedullin levels were measured from maternal and cord venous blood samples using a radioimmunoassay. Umbilical artery blood pH was also measured. RESULTS: There were no significant differences for maternal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. There were also no significant differences for fetal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. In the AGA group delivered vaginally, fetal mature/total adrenomedullin ratio (mean +/- standard error, 16.6 +/- 0.7%) was significantly higher than the maternal ratio (13.8 +/- 0.6%) (p < 0.05). In the SGA group delivered vaginally, fetal mature/total adrenomedullin ratio (18.5 +/- 1.0%) was also significantly higher than the maternal ratio (14.5 +/- 0.6%) (p < 0.05). There was no significant difference in umbilical artery blood pH among the groups. CONCLUSIONS: These results suggest that maternal and fetal plasma circulating adrenomedullin levels may play a role in maternal and fetal cardiovascular adaptation during delivery in pregnancies with both AGA and SGA infants.     

Comparison of umbilical blood gas and acid-base status of small-for-date and normal Chinese newborns.

A prospective study of umbilical arterial blood gas in appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) babies was performed at our hospital from August 1989 to July 1990. A total of of 512 cases were included, 432 cases in the AGA group and 80 cases in the SGA group, with gestational ages ranging from 26 to 42 weeks. Umbilical arterial blood was collected immediately after delivery of the newborns. Comparisons of maternal age, gestational age, birth body weight and body length of infants. Apgar scores at one minute and five minutes, cord arterial blood pH, pO2, pCO2, base excess, bicarbonate, total CO2, O2 saturation and O2 content between the AGA and SGA groups were taken into account. Our results demonstrated significant differences in birth body weight, birth body length, Apgar scores at one minute and five minutes and gestational age in the SGA group compared with those in the AGA group. The parameters of cord arterial blood gas were not correlated with gestational age in either group. The mean pH value in the AGA group (7.30 +/- 0.05) was higher than that in the SGA group (7.28 +/- 0.08). The same trend of difference was also noted between the AGA (7.30 +/- 0.04) and SGA (7.27 +/- 0.07) babies who were delivered by Cesarean section (p < 0.05). The latter results imply a more academic state in SGA babies which is independent of labor. Prepartum asphyxia plays an important role in determining the prognosis of SGA babies. We suggest routine umbilical cord blood gas and acid-base analysis at delivery to assess fetal asphyxia.     

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy

Objective.?To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET).

Methods.?Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P?<?0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET.

Results.?There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET.

Conclusions.?Maternal IGF-2 has a significant positive correlation with PET.     

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.     

Serum levels of leptin, insulin-like growth factor-I and insulin-like growth factor binding protein-3 in women with pre-eclampsia, and their relationship to insulin resistance.

The present study was carried out to compare serum levels of leptin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), homeostasis model assessment--(pancreatic beta-cell function) (HOMA-(%B)) and homeostasis model assessment--(tissue insulin sensitivity) (HOMA-(%S)) in women with mild and severe pre-eclampsia and normotensive pregnant women; and to evaluate the possible relationships between these parameters in the pathogenesis of pre-eclampsia. Seventy-three women were divided into three groups: group A consisted of 20 normotensive pregnant women (NPW); group B consisted of 25 women with mild pre-eclampsia (MPE); and group C consisted of 28 women with severe pre-eclampsia (SPE). Serum level of leptin was measured by enzyme immunoassay using a commercial kit. Serum levels of IGF-I and IGFBP-3 were measured with a two-site immunoradiometric assay. Serum level of insulin was measured by the electrochemiluminescence immunoassay method. HOMA used indices of pancreatic beta-cell function and tissue insulin sensitivity. Differences between groups were compared by one-way analyses of variance and the post hoc Tukey-HSD test for multiple comparisons; however, when a variable was not normally distributed, the Mann-Whitney U test was used. Associations between variables were tested using Pearson's coefficient of correlation. Birth weight was significantly lower (p < 0.001) in the MPE and SPE groups than in the NPW group. Serum levels of leptin and insulin in women with SPE and MPE were significantly higher (p < 0.001) than in NPW. Serum levels of IGF-I and IGFBP-3 were significantly lower in women with SPE and MPE compared with NPW (p < 0.001). The mean HOMA-(%B) level in women with SPE and MPE was significantly higher than in NPW (p < 0.001), whereas the mean HOMA-(%S) level in women with SPE and MPE was significantly lower than in NPW (p < 0.001). In the SPE group, systolic blood pressure correlated significantly with serum levels of IGF-I and leptin (r = 0.375, p < 0.05 and r = 0.495, p < 0.01, respectively). A negative correlation between mean HOMA-(%S) level and serum IGFBP-3 level was noted (r = -0.357, p < 0.05). There was a positive correlation between serum level of IGF-I and mean HOMA-(%B) level in mildly pre-eclamptic women (r = 0.541, p < 0.01). We conclude that pre-eclampsia is associated with insulin resistance; and that existing hyperinsulinemia and insulin resistance in women with pre-eclampsia seem not to correlate with leptin and birth weight, but may correlate positively with IGF-1 and IGFBP-3. Therefore we think that hyperleptinemia, low IGF-I or IGFBP-3, and insulin resistance may contribute to the pathogenesis of pre-eclampsia.     

Oral 17beta-estradiol and sequential progesterone in menopause: effects on insulin-like growth factors and their binding proteins.

OBJECTIVE: We evaluated the acute effects of low-dose oral estradiol and sequential progesterone on the insulin-like growth factor (IGF)/growth hormone (GH) axis, IGF-binding proteins (IGFBPs) 1 and 3, and plasma levels of sex hormone-binding globulin (SHBG) in postmenopausal subjects. STUDY DESIGN: Thirty healthy normal-weight women (mean age: 54.2 +/- 5.7 years) spontaneously postmenopausal for at least 6 months were enrolled. None had used hormone replacement therapy (HRT). Appropriate investigations excluded renal, glucose, lipid and coagulation abnormalities. Breast X-ray and endometrial ultrasound examinations excluded organic pathologies. They received oral cyclical HRT for 1 year, based on the administration of oral estradiol (1 mg/day) for 28 consecutive days plus progesterone (200 mg/day) from day 15 to day 28; out of the whole group, 15 subjects received progesterone orally (group A), while in 15 progesterone was administered transvaginally (group B). On the day before treatment (T0), on day 14 (T14) and on day 28 (T28) of the first cycle, plasma levels of estradiol, progesterone, SHBG, GH, IGF-I and -II, IGFBP-1 and -3, insulin and C-peptide were assayed in all patients. The same parameters were evaluated at T14 and T28 during the 12th month of treatment. RESULTS: At T14, we observed significant increases in the levels of estradiol (from 20 +/- 16 to 115 +/- 71 pg/ml, p < 0.001), SHBG (from 132 +/- 42 to 182 +/- 55 nmol/l, p < 0.001) and IGFBP-1 (from 92 +/- 57 to 127 +/- 87 ng/ml, p < 0.004), while the level of IGF-I decreased (from 197 +/- 138 to 129 +/- 85 ng/ml, p < 0.003). At T28, progesterone levels were significantly higher in the women receiving it orally than transvaginally (8.4 +/- 6.1 vs. 3.7 +/- 3.2 ng/ml, p < 0.025). However, while oral progesterone did not affect the estrogen-induced variations, transvaginal progesterone abrogated the increase in the levels of IGFBP-1. The levels of IGF-II, IGFBP-3, GH, glucose, C-peptide and insulin did not change at any time. At 1 year, the values maintained the same trends. The estrogen-induced variations of SHBG were correlated directly with those of estradiol (r = 0.48) and inversely with those of IGF-I (r = -0.424). CONCLUSIONS: Low-dose oral estradiol reduces plasma levels of IGF-I and increases IGFBP-1 and SHBG concentrations, while GH is unchanged. These effects, significant and immediate, lead us to hypothesize a direct action of estradiol on hepatocytes.     

胰岛素样生长因子I及其结合蛋白1对超排卵周期卵泡发育的影响

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Maternal insulin-like growth factor-I levels (IGF-I) reflect placental mass and neonatal fat mass

OBJECTIVE: This study was undertaken to test the null hypothesis that serial changes in maternal insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding-protein-1 (IGFBP-1) levels during pregnancy do not reflect differences in either corrected birth weight or placental mass at term.Study design Serial blood samples were obtained before pregnancy and at 8, 16, 24, 32, and 38 weeks from 56 healthy women enrolled in various exercise training regimens. Maternal, placental, and fetal morphometric parameters were monitored throughout. Enzyme-linking immunosorbent assays were used to determine IGF-I and IGFBP-1 levels. RESULTS: IGF-I and IGFBP-1 levels varied widely among the subjects at all time points, but there was a consistent fall in IGF-I levels in early pregnancy, followed by a rapid increase between 16 and 36 weeks' gestation, whereas IGFBP-1 levels rose in the first 16 weeks and were unchanged thereafter. The strongest linear correlations with morphometric outcome were between the increase in maternal IGF-I levels from 16 to 32 weeks and corrected birth weight (r(2)=0.27), neonatal fat mass (r(2)=0.65), and placental mass at term (r(2)=0.50). These were improved when maternal glucose level was included in a stepwise regression analysis (r(2)=0.50-0.70). CONCLUSION: There is a robust relationship among the rate of increase in individual maternal IGF-I levels after 16 weeks, placental mass, and neonatal fat mass. This does not imply causality but does indicate that midpregnancy changes in IGF-I levels may be a valuable marker for anomalous fetal growth.     

Maternal hemodynamics and impaired fetal growth in pregnancy-induced hypertension

Twenty-one subjects with pregnancy-induced hypertension were investigated with regard to the relationship between maternal hemodynamics and fetal growth. Five of the infants were small for gestational age (SGA) (less than tenth percentile) and 16 were appropriate for gestational age (AGA) (greater than tenth percentile). Mean arterial blood pressure, cardiac output, and stroke volume were significantly lower in the group of mothers with SGA infants than in the group with AGA infants (102 +/- 3 versus 115 +/- 3 mmHg, 5.8 +/- 0.2 versus 8.2 +/- 0.3 L/minute, and 76 +/- 7 versus 100 +/- 5 mL, respectively). The results of this investigation suggest that the hemodynamic background to the blood pressure increase in pregnancy-induced hypertension ranges from a low cardiac output, high vascular resistance condition to a high-output, low-normal resistance variant. The former subtype is often associated with the birth of an SGA infant.