Effect of gestational age upon prealbumin and retinol binding protein in preterm and term infants

The relationships between maternal and umbilical cord levels of prealbumin and retinol binding protein (RBP) were studied in 68 mothers and in their appropriate-for-gestational-age neonates delivered between 25 and 42 weeks gestation. Arterial and venous concentrations of prealbumin and RBP in cord sera were also studied in a subsample of eight infants. In cord sera, prealbumin and RBP levels increased with gestational age (prealbumin, r = 0.47; RBP, r = 0.40, p less than 0.01), and were significantly different in neonates born at term compared to those born prematurely (mean +/- SD, prealbumin 12.0 +/- 3.9 mg/dl vs. 8.8 +/- 2.3 mg/dl, p less than 0.001; RBP, 2.3 +/- 0.8 vs. 1.8 +/- 0.5 mg/dl, p less than 0.005). No significant differences between arterial and venous concentrations of prealbumin and RBP were observed in cord blood. In maternal blood, serum prealbumin and RBP concentrations did not increase with length of gestation (25-42 weeks). Maternal prealbumin was not correlated significantly with infants' cord serum levels; the correlation coefficient for RBP was 0.29, p less than 0.05. Maternal prealbumin and RBP serum levels were approximately twice the values seen in neonates born both at term and prematurely. Although the difference between premature and full-term cord levels of prealbumin and RBP may reflect an increase in hepatic protein synthesis that occurs with maturation of the fetus and/or a change in placental function after 37 weeks gestation, neither of these factors sufficiently explains the variance in neonatal prealbumin and RBP levels.     

Serum somatomedin C, bioassayable growth-promoting activity (thymidine activity), and transferrin in human fetuses: in utero study

Serum somatomedin C, thymidine uptake stimulating activity, and transferrin were measured in fetal blood collected by ultrasound-guided puncture of umbilical vessels in utero during prenatal assessment for mother-to-fetus transmissible infections. Serum somatomedin C and transferrin were measured by immunoassay. Thymidine activity was measured by assay of [3H]thymidine incorporation into lectin-activated human lymphocytes. Studies were conducted in 48 healthy fetuses at gestational ages 21-28 wk. From 21-24 to 25-28 wk, serum somatomedin C significantly increased from 0.05 +/- 0.06 to 0.24 +/- 0.03 U/ml, while thymidine activity significantly decreased from 1.41 +/- 0.15 to 0.95 +/- 0.06 U/ml. Transferrin levels did not change. These data suggest that the humoral control of fetal growth at midpregnancy involves mechanisms other than direct regulation by somatomedin.     

Somatomedin activity in human cord plasma and relationship to birth size,insulin, growth hormone,and prolactin

Somatomedin activity was determined by a rabbit chondrocyte bioassay in cord plasma from babies of between 37 and 41 wk gestation. A positive correlation (P<0.001) was found between plasma somatomedin activity and birthweight. The mean somatomedin activity in infants whose birthweights were within 1 SD of the mean (3293 g) was 0.76 ± 0.27 U/ml. Mean somatomedin activity in infants whose weight was (a) greater than the mean weight ± 1 SD was 1.3 ± 0.17 U/ml, and (b) less than the mean weight ? 1 SD was 0.48 ± 0.15 U/ml. Plasma somatomedin activity was also correlated with placental weight, P< 0.02 and gestational age, P<0.05. No correlation was found between plasma somatomedin activity and birth length, OFC, most measurements of skinfold thickness, cord plasma, growth hormone, prolactin or insulin.     

脑源性神经营养因子与新生儿出生体重的关系

目的：该文通过检测新生儿脐血脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）的水平,探讨BDNF与新生儿出生体重的关系,并对相关因素进行分析。方法：根据出生体重,将51 例足月第1胎健康新生儿分为3 组:①小于胎龄组（SGA）8例;②适于胎龄组（AGA ）31例;③大于胎龄组（LGA）12例。测量新生儿身长、体重及其母亲的身高、体重,并对脐血中BDNF、瘦素（LEP）、胰岛素（INS）、总胆固醇（TC）、甘油三酯（TG）进行检测。结果：SGA组的BDNF明显高于AGA组和大于LGA组,AGA组和LGA组中BDNF没有差异;多元逐步回归分析显示BDNF值与新生儿出生体重、体重指数存在负相关关系。LEP与BDNF不呈相关趋势（P>0.05）,INS与BDNF也不呈相关趋势（P>0.05）。INS 与LEP呈现正相关（P<0.05）。LEP与新生儿体重、产妇体重及其BMI呈正相关,而TC,TG在3组新生儿中差异无显著性。结论：BDNF是新生儿体重的重要影响因素,而且不受LEP,INS的影响。     

N-terminal propeptide of type-III procollagen concentrations in the cord blood: an index of newborn maturity

Cord serum concentrations of the N-terminal propeptide of type-III procollagen(PIIIP), insulin-like growth factor I (IGF-I), thyroid-stimulating hormone (TSH) and free thyroxine were measured in 149 neonates, consisting of 22 small for gestational age, 95 appropriate for gestational age, 21 large for gestational age and 11 neonates of less than 24 weeks of gestation. Their gestational ages (GAs) ranged from 20 to 41 weeks. A significant negative correlation was found between PIIIP levels and GA (r = -0.83, p less than 0.001). No significant difference was found in PIIIP levels between SGA and LGA neonates, when there were no difference in their GAs, in spite of a significant difference in their birth body weights (p less than 0.01). The high concentrations of the cord serum PIIIP did not appear to be influenced by either IGF-I or thyroid hormones, nor was there any relationship between PIIIP and the birth body weight, but only with GA, suggesting that determining cord levels of PIIIP seems to provide a useful parameter for the assessment of newborn maturity.     

Serum growth-promoting activity in normal and hypotrophic fetuses at midpregnancy

Blood from 24 human fetuses aged 19-24 wk was collected by ultrasound-guided puncture of the umbilical cord in utero, performed for prenatal diagnosis of mother to fetus transmissible infections. Fetal serum growth-promoting activity (thymidine activity) was measured by its effect on 3H-thymidine incorporation into human lectin-activated lymphocytes. Ten blood samples were obtained at 19-22 wk of pregnancy and 14 at 23-24 wk. The pregnancies were maintained and the fetuses delivered, free of infection, at 38-40 wk, nine of them being small for date and 15 having a normal weight for gestation age. The bioassayable thymidine activity was significantly lower in the hypotrophic (0.84 +/- 0.04 U/ml) than in the normal fetuses (1.28 +/- 0.09 U/ml) whatever the time of sampling. Thymidine activity was significantly negatively correlated with gestational age in the normal for date fetuses, not in the small for date. It is suggested that early measurement of thymidine activity in fetal blood might be of value in the assessment of fetal growth despite the fact that the tissue growth factors may be more important in fetus than are the serum factors.     

The relationship of the levels of leptin, insulin-like growth factor-I and insulin in cord blood with birth size, ponderal index, and gender difference

In humans, serum levels of leptin correlate with total body fat in both adults and children. After collecting cord blood from 156 term neonates (82 males, 74 females; 132 AGA and 22 LGA), we measured the cord levels of leptin, insulin and IGF-I to determine the relationships between these three hormones and relationships of these hormones with birth size (birth weight and ponderal index for adiposity in newborn) and gender. The leptin and IGF-I levels were significantly higher in the LGA group (9.2+/-4.0 ng/ml and 96.1+/-34.1 ng/ml, respectively) than in the AGA group (4.8+/-3.8 ng/ml and 56.4+/-37.6 ng/ml, respectively). A significant positive correlation was observed between leptin levels and birth weight, and a weaker correlation between leptin levels and birth height. IGF-I level significantly correlated with birth weight and birth height, but there was no correlation between the levels of insulin and birth weight. There was no relationship between the levels of IGF-I, insulin and leptin. Ponderal index was higher in LGA than in AGA. A significant correlation was also observed between the levels of leptin and ponderal index, but not between the levels of insulin or IGF-I and ponderal index. The levels of leptin and ponderal index were higher in females than males despite no gender differences in gestational age and birth weight. In conclusion, our results suggest that the level of IGF-I is a useful index for fetal growth during late gestation, and the development of adipose tissue is the major determinant of fetal serum leptin levels, the production of which is not regulated by insulin or IGF-I. In addition, a gender difference with a higher level of leptin in female neonates suggests that sexual dimorphism in adipose tissue already exists in utero.     

新生儿脐血Toll样受体变化及其意义

目的观察新生儿脐血单个核细胞（MNC）rrLR4、TLR2mRNA的表达。方法将46例无窒息新生儿及40例窒息新生儿根据胎龄分组,分离脐血MNC,测定其TLR4／2mRNA表达及上清中TNF-α水平。另外将TLR4／2mRNA表达水平与TNF-α水平进行相关分析。结果无窒息新生儿中足月儿TLR4／2mRNA及TNF-O／．水平分别为0．75±0．12、0．63±0．08、2502．6±273．1ng／t,胎龄≥32周但〈37周早产儿分别为0．37±0．04、0．32±0．03、1218．8±145．7ng／t,胎龄〈32周早产儿分别为0．26±0．03、0．20±0．03、811．8±105．2ng／t;窒息新生儿中足月儿TLR4／2mRNA及TNF-α．水平分别为0．58±0．07、0．50±0．06、1946．4±244．2ng／t,胎龄≥32周但〈37周早产儿分别为0．29±0．03、0．26±0．03、970．0±94．3ng／t,胎龄〈32周早产儿分别为0．17±0．02、0．14±0．02、652．6±60．3ng／t;成人TLR4／2mRNA及TNF-α水平分别为2．71±0．75、2．61±0．33、9270．1±1098．3ng／t。早产儿、足月儿TLR4／2mRNA及TNF-α水平均低于成人,胎龄越低,TLR4／2mRNA及TNF-α水平越低。窒息新生儿TLR4／2mRNA及TNF-α的表达水平均低于同胎龄无窒息新生儿（P〈0．01）。TLR4／2mRNA表达水平与TNF-O／．水平呈正相关关系。结论新生儿,特别是早产儿,TLR水平低下,可能是新生儿天然免疫能力低下,容易患败血症等严重感染性疾病的重要原因之一。     

Bone gamma-carboxyglutamic acid containing protein in the perinatal period

We measured bone gamma-carboxyglutamic acid-containing protein (BGP), calcium (Ca), phosphorus (P), and alkaline phosphatase (Al-P) in paired maternal and cord sera, and urinary gamma-carboxyglutamic acid (gamma-Gla) in neonates. The circulating BGP was 41.21 +/- 2.47 ng/ml and 7.44 +/- 0.87 ng/ml in the cord (n = 15) and the maternal (n = 14) sera, respectively. The urinary gamma-Gla in the neonates was 147.68 +/- 10.75 mumol/g creatinine (n = 15). The cord serum BGP was significantly higher than the normal adult level. The maternal serum BGP was at the same level as in other adults. It is conceivable that the fetus may produce BGP during gestation, as the cord serum BGP level was significantly higher than the maternal level and there was no correlation between the cord and maternal serum BGP concentrations. The reason for the elevated circulating BGP level in the cord serum is not known, but increased bone turnover may be a factor. The cord serum BGP may include not only carboxylated but also non-gamma-carboxylated GP because of fetal vitamin K deficiency.     

不同胎龄儿脐血IGF-1、IGFBP-1及CP水平的变化

目的 了解胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-1(IGFBP-1)及C肽(CP)对不同胎龄新生儿出生体重的影响。方法 选取不同胎龄的新生儿共76例,按孕周分为≤32、-34、-36、-38、-40、-42周6组,均为适于胎龄儿。分娩时取脐静脉血3 ml,用EIASA法测定血清IGF-1、IGFBP-1及CP。结果 自32周至40周,血清IGF-1、CP逐渐增加,IGFBP-1逐渐下降,各组间差异有显著意义(除34与36周三者比较P>0.05外),但至42周时,IGF-1、CP开始下降,IGFBP-1上升,与40周相比,P<0.05。IGF-1、CP均与胎龄呈中度正相关,而IGFBP-1与胎龄呈高度负相关。结论IGF-1、CP能促进孕晚期胎儿宫内生长,而IGFBP-1则对胎儿生长起抑制作用。因此,营养物质-胰岛素-胰岛素样生长因子系统代谢轴是孕后期调节胎儿生长的重要系统。     

Resistin in Cord Blood of Small for Gestation Age and Appropriate for Gestation Age Term Neonates

Objective

Placental hormones such as resistin, adiponectin, ghrelin and leptin are known to have considerable role in fetal growth and there are some articles published in this area recently. Nevertheless there is a shortage of data showing association between resistin level and fetal growth; that was why we decided to conduct a study to evaluate this association.

Methods

This study was approved by ethic committee of pediatric health research center and research vice chancellor of Tabriz University of Medical Sciences. In this case-control study we measured the insulin, glucose and resistin in the cord blood of neonates with gestational age of 37 weeks or more in Al Zahra tertiary hospital from March 2011 to March 2012. Thirty-nine appropriate for gestation age (AGA) neonates and 41 small for gestation age (SGA) neonates were studied.

Findings

The umbilical cord blood resistin level was not found to have significant correlation with the type of delivery [normal vaginal delivery (NVD) or cesarean-section (C-S)], neonate’s gender, maternal age or body mass index (BMI). There was no significant difference in the levels of Insulin and glucose between AGA and SGA groups. Resistin level of blood cord in AGA group was 613.76±180.10 (range: 132.6-983.80 ng/ml) and in SGA group it was 1303.47±537.07 (range: 800.9-3001 ng/ml) (P<0.001). Neonates’ weight in AGA group was 3162.82±407.92 g and in SGA group it was 2425.85±32.84 g (P<0.001).

Conclusion

In this study resistin level had reverse correlation with fetal weight in term neonates. The SGA neonates with growth insufficiency have higher resistin levels in their cord blood than AGA neonates with same gestational age. It is recommended to conduct more studies in future with larger population of patients to clarify the resistin role in neonatal birth weight.     

Effect of bromocriptine treatment on circulating somatomedins in tall adolescents

Somatomedin and bromocriptine levels were measured before and after 3 months of bromocriptine treatment (5 mg/day) in the sera of 16 tall adolescents with excessive adult height prediction. Somatomedins were measured by RIA for somatomedin C and IgFII and by measuring thymidine incorporation into human lectin-activated lymphocytes. Mean +/- SEM levels of bromocriptine after three months of treatment were 0.61 +/- 0.08 ng/ml. No changes in radioimmunoassayable somatomedin C were observed after bromocriptine intake respectively 1.34 +/- 0.17 U/ml before and 1.4 +/- 0.01 U/ml during treatment. On the opposite a significant decrease of thymidine activity (p less than 0.002) from 1.45 +/- 0.17 U/ml to 1.12 +/- 0.19 U/ml was observed. No changes of IgFII levels were observed in the sera of the 8 patients where they were measured. In order to test a possible direct effect of bromocriptine on peripheral tissues bromocriptine mesylate was added in somatomedin bioassays. Inhibitory effect of bromocriptine in vitro is seen at higher levels (1 microM) compared to the circulating one (1 nM). This study demonstrates that the major effect of bromocriptine which is the acceleration of bone maturation is not related to changes in somatomedin C.     

Prolactin in umbilical cord blood and the respiratory distress syndrome.

Prolactin was measured in umbilical cord serum obtained from 77 newborn infants of gestational age 28 to 40 weeks. A positive correlation with gestational age was demonstrated. Between 30 and 36 weeks of gestation the elevation of the regression line of the concentration of cord PRL versus gestation age was significantly lower (P less than 0.05) for those infants who developed respiratory distress syndrome compared to the regression line for infants who did not develop RDS. Between 32 and 33.5 weeks, the mean +/- SEM cord PRL concentration in infants who developed RDS (101.7 +/- 9.5 ng/ml) was significantly less (P less than 0.025) than the PRL concentration in those who did not develop RDS (161.8 +/- 18.9 ng/ml). Cord PRL did not correlate with cord cortisol or dehydroepiandrosterone sulfate concentrations. Cord growth hormone concentrations did not show any relationship to the occurrence of RDS. Serum PRL was not suppressed in a further 114 infants whose mothers were treated prenatally with betamethasone. These findings raise the possibility of a role of PRL in fetal lung maturation.     

Red cell oxygen affinity, hemoglobin type, 2,3-diphosphoglycerate, and pH as a function of fetal development.

Studies were carried out on fresh cord blood obtained at delivery from nonstressed normal fetuses ranging from 24 to 42 weeks of gestation, to determine the relationship of 2,3-diphosphoglycerate (DPG), the intracellular red cell and extracellular pH, and the proportions of adult and fetal hemoglobin in regulating the position of fetal red cell oxygen affinity in utero. There was a significant positive correlation between P50 and gestational age (r = .62, P less than .001), the linear regression increased from 17.8 to 22.5 mm Hg. There was also a significant positive correlation between P50 and the percentage of adult type hemoglobin (HbA) (r = .67, P less than .001). In contrast gestational age had no effect of 2,3-DPG levels, the mean and SD was 14.86 +/- 2.04 mol/gm of Hb or delta pH between plasma and red cell, the mean was 0.187 +/- SD 0.032. However, there was a significant negative correlation between the intraerythrocyte hydrogen ion concentration and DPG level (r = .5, P less than .025). It is concluded therefore that the decrease in fetal oxygen affinity as gestation progresses is related mainly to the increase in the amount of HbA and the levels of DPG or delta pH between plasma and red cells are not a function of gestational age.     

Observational study of maternal anthropometry and fetal insulin.

AIMS: To examine the relation between maternal body fat and fetal metabolism. METHODS: In this observational study, cord blood samples were collected from 60 infants of healthy women for the measurement of insulin and C peptide concentrations. Maternal weight, height, body mass index (BMI) and body composition (skinfold thickness measurements and bioelectrical impedance) were assessed at 13-15 weeks of gestation. Twenty five of the volunteers agreed to have a 75 g oral glucose tolerance test at 28-31 weeks of gestation. RESULTS: Positive correlations were observed with both cord insulin or C peptide concentrations and maternal early pregnancy BMI (r=0.44, p=0.002 and r=0.33, p=0.008, respectively). There was no significant correlation between cord insulin or C peptide concentrations and birthweight or birth weight centiles. CONCLUSION: Maternal BMI could be a predictor of fetal cord insulin concentration.     

Serum growth-promoting activity in human newborns. Relationship of thymidine activity with birth weight and the length of gestation

Thymidine Activity (TA) was measured by the effect of serum upon incorporation of 3H-thymidine into human lectin-activated lymphocytes in 54 newborns: 32 full-term, 11 pre-term and 11 with intra-uterine growth retardation (IGR). Capillary blood was collected at 0-6 hours, with routine samplings. TA values were lower in preterm (0.476 +/- 0.079 U/ml) than in IGR (0.910 +/- 0.118 U/ml, p less than 0.01) and in full-term neonates (1.237 +/- 0.60, p less than 0.001), and also in IGR newborns than in newborns of normal weight (p less than 0.025). In preterm neonates TA was significantly correlated with gestational age (r = 0.715, p less than 0.02), but no such correlation existed in IRG and full-term neonates. When TA values were plotted against birth weight, a correlation was found in preterm (r = 0.715, p less than 0.02) and in IGR newborns (r = 0.714, p less than 0.02), but not in full-term neonates. Longitudinal study up to 21 days did not show significant changes in full-term newborns, while in preterm and IGR neonates TA increased progressively to reach normal values at the 21st day. The correlations observed in newborns between TA, birth weight and gestational age, and the postnatal normalization in newborns with low birth weight, show that TA directly reflects the nutritional state of the fetus.     

Serum vitamin A in premature and term neonates

Serum vitamin A was determined in premature and term neonates by a specific spectrofluorometric method. Premature neonates (N = 42; gestational age = 32 +/- 0.4 weeks) had a serum vitamin A level (14.9 +/- 0.98 microgram/dl) significantly lower (P less than 0.001) than that of term neonates (N = 51; 22.4 +/- 0.99 microgram/dl). The vitamin A mean serum values of infants of 36 weeks' gestational age were not statistically different from those of the term neonates. Linear regression analysis for serum vitamin A values vs gestational age showed no significant correlation. A linear correlation (P less than 0.05), however, was found between serum vitamin A and serum protein protein concentrations, perhaps indicative of a lower concentration of retinol-binding protein. Since vitamin A is involved in the promotion of mucous-secreting cells, the premature neonate may be at greater risk than the term infant for diseases involving the mucosal epithelium, including necrotizing enterocolitis.     

Stool water loss in very-low-birth-weight neonates

Fluid requirements in very-low-birth-weight (VLBW) infants include compensation for renal, insensible (skin and lung), and stool losses and provision for fluid retained for growth. Current estimates of stool water losses in VLBW infants are based on measurements established in term neonates. Therefore, the water content of 24-hour stool collections were determined in 11 healthy VLBW male infants on full enteral feeds and compared to the working norms. The neonates in this study were less than 2 weeks old with a mean +/- SD birth weight and gestational age of 1,311 +/- 112 g and 30.8 +/- 1.5 weeks, respectively. They were receiving only enteral formula feedings of 100 ml/kg/day or more with no parenteral fluid supplementation. The mean +/- SD number of stools and water content of the stools was 2.7 +/- 2.0/day and 7.2 +/- 4.0 ml/kg/day, respectively. There was a significant correlation (r = 0.696, p less than 0.02) between gestational age at birth and number of stools per day, but the correlation between stool water loss per day, gestational age, volume of feedings per day, and birthweight was not significant. Based on this study, 7 ml/kg/day is a reasonable estimate of daily stool water loss in VLBW babies.     

Serum level of digoxin-like immunoreactive substances in newborn infants in the first two weeks of life, in umbilical cord blood and in pregnant patients at the time of labor

A digoxin-like immunoreactivity (DLIS) was measured by two routinely used clinical digoxin-immunoassays (radio- and enzymeimmunoassay) in cord blood of 255 newborns, in sera of their mothers at birth and in sera of 211 newborns during the first two postpartal weeks. The highest DLIS levels were found in serum of neonates at the first day of life (median: 0.23 ng/ml, 25% and 75% percentile: 0.19 and 0.28 ng/ml) and in cord blood (median: 0.21 ng/ml, 25% and 75% percentile: 0.19 and 0.24 ng/ml); maternal serum was shown to have three times less DLIS (median: 0.08 ng/ml, 25% and 75% percentile: 0.05 and 0.10 ng/ml). There was no significant correlation between DLIS concentrations in serum of newborns, cord blood or pregnants. The DLIS serum levels of preterms with birthweight less than 2500 g and gestational age less than 37 weeks were significantly lower than those of normal neonates at term (p less than 0.01); concomitantly the lowest DLIS levels were found in maternal serum of preterms (p less than 0.01). These observations strongly suggest rather a DLIS origin in the newborn than in the mother. During the first two postpartal weeks the DLIS concentration of a vast majority of the 211 newborns (91%) decreased continuously to one half of the starting value. Within the second postpartal week preterms were found to have a significantly delayed decrease in the DLIS serum levels (p less than 0.01). Small for date newborns showed no difference in their postpartal DLIS time course compared to normal neonates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anterior lens capsule vascularity in evaluating gestation in small for gestation neonates

This study evaluated the role of anterior lens capsule vascularity in assessing gestation in small for gestational age (SGA) neonates in a prospective manner. Neonates with birth weight less than 2000 g were recruited. Those with gross congenital malformations, including corneal opacity or cataract and evidence of TORCH infection were excluded from the study. A total of 139 subjects were enrolled into the study (60-appropriate for gestational age (AGA) and 79 small for gestational age (SGA) neonates). Clinical gestational age assessment and ophthalmoscopic examination for anterior lens capsule vascularity grading were done within 24 hours of birth by independent blinded observers. The correlation of lens capsule grading with clinical gestation in AGA neonates (r2 = 0.75) was stronger compared to SGA neonates (r2 = 0.50). Gestational age assessment by lens capsule grading had a better agreement with clinical gestation in AGA subjects (Kappa Index - 0.56 in AGA vs. 0.26 in SGA). The lens capsule grading under-estimated the gestation of SGA subjects by an average of three weeks compared to AGA neonates.