新生儿血清瘦素水平与生长发育关系研究

目的：探讨新生儿血清瘦素与生长发育的关系。方法：采用放射免疫法检测80例新生儿静脉血和脐血瘦素水平,其中66例足月儿分为大于胎龄儿(LGA)组18例,适于胎龄儿(AGA)组32例,小于胎龄儿(SGA)组16例。采用Rohrer’s指数=出生体重(g)×100/身长(cm)~3估测新生儿营养状态。结果：早产儿血清瘦素水平明显低于足月儿[(0.66±1.03)ng/ml vs(3.59±2.16)ng/ml],P<0.01;足月儿中AGA血清瘦素水平[(3.06±0.96)ng/ml]明显低于LGA[(4.03±2.22)ng/ml],而高于SGA[(1.13±1.98)ng/ml];足月新生儿血清瘦素水平与Rohrer’s指数、新生儿体重、胎龄呈显著正相关(r=0.61,0.68,0.62,P均<0.01)。结论：新生儿体内瘦素是反映新生儿的发育和营养状态的有用指标。[中国当代儿科杂志,2003,5(1):29-30]     

Maternal insulin-like growth factor binding protein-1, body mass index, and fetal growth

AIM: To examine the hypothesis that the maternal insulin-like growth factor system may constrain fetal growth. METHODS: A prospective observational study of maternal serum insulin-like growth factor binding protein-1 (IGFBP-1) and fetal growth was undertaken in neonates with birthweights below the 5th centile. They had been classified either as having fetal growth restriction (FGR) due to placental dysfunction (increased umbilical artery Doppler pulsatility index (PI); n = 25) or as being small for gestational age (SGA; normal umbilical artery PI, growth velocity and amniotic fluid; n = 27). Eighty nine controls had normal birthweights (5th-95th centile), umbilical artery PI, growth velocity, and amniotic fluid. IGFBP-1 was measured by radioimmunoassay. RESULTS: Among the controls, there was no significant correlation between IGFBP-1 and birthweight after allowing for body mass index (BMI). Maternal BMI was high in FGR and after adjusting for this, IGFBP-1 was increased (109 ng/ml) compared with SGA babies (69 ng/ml) and controls (57 ng/ml) and correlated with the umbilical artery PI. CONCLUSIONS: Maternal IGFBP-1 is probably not part of normal placental function. Its increase in FGR could be the cause or consequence of impaired placental perfusion, but high IGFBP-1 concentrations might further reduce the availability of maternal IGF-I to the placenta. This could worsen placental function and so adversely affect fetal growth.     

Effect of maternal diabetes on the fetal exocrine pancreas

To test the hypothesis that fetal pancreatic exocrine and endocrine function are stimulated in parallel in the diabetic pregnancy, 68 mothers with gestational and pregestational diabetes who underwent amniocenteses after 34 weeks' for the evaluation of fetal lung maturity were enrolled. Amniotic fluid specimens were analyzed for C-peptide and trypsin content. Amniotic fluid specimens were obtained from 92 non-diabetic women undergoing amniocenteses for lung maturity, preterm labor, or premature rupture of membranes. Groups were compared using the Wilcoxon rank-sum test, Kruskal Wallis rank sum test, and Spearman's rank correlation test. C-peptide amniotic fluid concentrations were significantly greater in diabetics (median 0.6 ng/ml) than non-diabetics (median 0.4 ng/ml, P= 0.0001), in pregestational (median 0.6 ng/ml) vs. gestational diabetics (median 0.4 ng/ml, P = 0.006), and greater in proportion to severity of disease according to diabetic class (A1 = 0.4 ng/ml, A2 = 0.55 ng/ml, B = 0.6 ng/ml, C = 0.7 ng/ml, D = 0.85 ng/ml, P = 0.04). No significant differences were detected in amniotic fluid trypsin between the diabetic and non-diabetic or the gestational and non-gestational diabetic groups. There was no correlation between C-peptide and trypsin within the diabetic groups. Stimulation of the exocrine and endocrine pancreas does not occur in parallel in the fetus of the diabetic mother. Although originating as a single organ, pancreatic exocrine and endocrine functions are distinct in both physiologic and pathologic conditions.     

脐血可溶性瘦素受体与胎儿生长发育关系探讨

目的：瘦素是肥胖基因的蛋白产物,除参与调节机体能量代谢外,与胎儿的生长发育密切相关,但其作用机制尚不清楚。本研究旨在探讨脐血可溶性瘦素受体与胎儿生长发育的关系及其可能机制。方法：67例足月新生儿根据出生体重分为小于胎龄儿(SGA)组23例,适于胎龄儿(AGA)组44例。采用ELISA法测定脐血和母血中瘦素及可溶性瘦素受体水平,并采用体脂含量估测新生儿营养状态。结果：①脐血可溶性瘦素受体水平与脐血瘦素水平及新生儿出生体重、体脂含量呈负相关(r分别为-0.405,-0.366,-0.356,P均0.05)。③SGA组脐血可溶性瘦素受体明显高于AGA组［(18.24±6.02) ng/ml vs (13.80±4.37) ng/ml］,P<0.01;而SGA组的瘦素含量低于AGA组［(6.79±4.59) ng/ml vs (16.30±11.62) ng/ml］,P<0.01。④脐血可溶性瘦素受体水平男性高于女性［(16.89±4.37) ng/ml vs (13.95±5.29) ng/ml］,P<0.05;而脐血瘦素水平则是男性低于女性［(10.28±8.28) ng/ml vs (15.70±12.11) ng/ml］,P<0.05。结论：可溶性瘦素受体可能通过对血清中游离瘦素水平的调节实现对胎儿生长发育的调控作用。同时测定瘦素和可溶性瘦素受体可能更有利于进一步了解瘦素的病理生理作用机制。     

The concentration of the 35-kDa surfactant apoprotein in amniotic fluid from normal and diabetic pregnancies

A specific, enzyme-linked immunoabsorbent assay was used to determine the concentration of the 35,000 mol wt surfactant apoprotein (SP-A) in samples of amniotic fluid obtained from nondiabetic (n = 358) and diabetic (n = 29) women. The enzyme-linked immunoabsorbent assay was performed with rabbit antibodies directed against SP-A present in lavage fluid from a patient with alveolar proteinosis. Amniotic fluid SP-A concentrations increased as a function of gestational age, from less than 3 micrograms/ml at 30-31 wk to 24 micrograms/ml at 40-41 wk, and were positively correlated with the lecithin to sphingomyelin ratio (p less than 0.01). SP-A concentrations also increased as a function of gestational age in shake test positive samples (p less than 0.05), but were unchanged in shake test-negative samples. There was no difference in the surfactant apoprotein concentration of male compared with female fetuses at any gestational age. In amniotic fluid obtained from 20 diabetic women, SP-A levels were significantly less than in nondiabetic pregnancies that were matched for gestational age and sex of the fetus (p less than 0.05). The SP-A concentrations in amniotic fluids obtained from nine women who were diabetic and hypertensive and from 10 hypertensive women were not different from matched controls. The relationships described above were valid whether the SP-A concentration was expressed per mg protein or per ml amniotic fluid. These data are suggestive that the concentration of amniotic fluid SP-A is decreased in diabetic pregnancies.     

肺出血新生儿血中一氧化氮和内皮素-1水平变化及意义

目的 研究一氧化氮(NO)和内皮素-1(ET-1)在肺出血新生儿血中的变化及其与预后的关系。方法 用硝酸还原酶法和放射免疫法分别测定对照组(n=15),肺出血存活极期组(存活组,n=13),肺出血恢复期组(恢复组,n=3)和肺出血死亡组(死亡组,n=7)四组新生儿血中NO和ET-1的水平。结果 对照组,存活组,恢复组和死亡组的NO水平分别为63.0±10.7umol/L,32.0±7.5umol/L,68.2±6.9umol/L和20.1±5.2umol/L;ET-1水平分别为19.6±4.0 ng/L,43.0±8.9ng/L,20.7±4.5ng/L和54.1±3.9ng/L;NO/ET-1比值分别为3.21,0.74,3.29和0.37。NO与ET-1浓度之间呈负相关,r = -0.79 (P<0.01)。各组之间差异有显著意义(P<0.01或P<0.05)。结论 肺出血新生儿血中NO降低,ET-1升高,二者呈负相关,NO／ET-1比值降低与疾病严重程度密切相关,后者可作为肺出血患儿预后估计的指标。     

Color of Meconium and Interleukin-6

Objective

To test the hypothesis that the color of meconial fluid is associated with inflammatory biomarkers, by determining C-reactive protein (CRP) and Interleukin-6 (IL-6) in serum from the umbilical cord.

Methods

In this prospective study, the authors selected 30 newborns with meconium-stained amniotic fluid (MSAF): 14 with green/brown 656 R color and 16 with brown/cinnamon 654 R color, and 20 newborns which showed clear amniotic fluid without MSAF (non-MSAF); all newborns were from mothers without risk factors for neonatal sepsis.

Results

IL-6 concentration from umbilical cord blood, [median of 12.9?pg/mL (interquartile range {IQR} 8.7?C31.0)] of MSAF-green/brown 656 R increased significantly (p?<?0.05) when compared with IL-6 concentration, [median of 9.2?pg/mL (IQR 7.2?C12.2)] of newborns with clear amniotic fluid and without meconium. CRP from MSAF-green/brown 656 R was median of 0.5?mg/mL (IQR 0.0?C2.7), and median of 1.0?mg/mL (IQR 0.0?C5.5) from clear amniotic fluid, without meconium.

Conclusions

Significant association was found between MSAF-green/brown 656 R and increase in IL-6, with normal CRP values.     

Alpha1-fetoprotein: physiology, pathology and diagnosis especially in childhood (author's transl)]

Alpha1-fetoprotein (AFP) is an alpha1-glycoprotein which can be found in high concentration during fetal development in many mammals, birds, sharks and, also, man. The alpha-fetoproteins of various species have similar physico-chemical properties and often common antigenic determinants. Differences of microheterogeneity depend on a different content of sialin-acid. During human fetal development the serum AFP concentration falls with increasing gestational age. 4-5 weeks after birth AFP can be detected usually in low serum concentrations. Using more sensitive immunulogic techniques e.g. radioimmunoassay there was shown that AFP is present in sera of normal adults in concentrations of 10-20 ng/ml. AFP serum concentrations rise physiologically during pregnancy up to 500-550 ng/ml. During fetal development liver, yolk sac and gastrointestinal tract are the major sites of synthesis. In primary liver cell carcinoma, hepatoblastoma and in teratoblastoma containing yolk sac tissue AFP synthesis rises in tumor cells; the AFP serum concentration increases above 2 microgram/ml. In patients with benign liver diseases e.g. virus hepatitis, a transient rise of AFP serum concentrations was seen. Moreover, increased levels of AFP were found in hereditary diseases e.g. congenital tyrosinemia, ataxia-telangiectasia and in the amniotic fluid in congenital nephrosis of Finnish type. AFP assay in serum is clinically important for the control of course and treatment of primary liver cell carcinoma and teratoblastoma. AFP assay in amniotic fluid is a method for the prenatal detection of neural tube defects and the fetal distress syndrome, especially.     

IGF-I, IGF-II, IGF binding protein 1, and C-peptide in second trimester amniotic fluid are dependent on gestational age but do not predict weight at birth.

Previous data suggested that small for gestational age newborns have increased levels of IGF binding protein 1 (IGFBPI) in amniotic fluid (AF) at 15-16 wk of pregnancy. In this study, we developed an RIA for IGFBP1 and measured IGFBP1 concentrations in 209 AF samples with normal fetal karyotype between 14 and 20 wk; we measured IGF-I, IGF-II, and C-peptide in the same samples. Concentrations of these growth-modulating factors were all positively correlated with gestational age at sampling (p < 0.0001). After correcting for gestational age, AF IGFBP1 remained strongly correlated with IGF-I and IGF-II (both p < 0.0001); their concentrations were many times higher in AF than in cord serum during the third trimester. None of the growth-modulating factors in AF correlated with birth weight, after correction for gestational age; birth weight percentile distribution was comparable in two groups of newborns who had AF values of IGF-I, IGF-II, IGFBP1, or C-peptide that were either less than or equal to the 50th percentile or more than the 50th percentile at sampling. However, placenta weight and the placenta weight to birth weight percentage were negatively correlated with AF IGF-I, IGF-II, and IGFBP1; placenta weight to birth weight percentage was lower in pregnancies with IGFBP1 values more than the 50th percentile compared with those less than or equal to the 50th percentile at sampling. In conclusion, AF concentrations of IGFBP 1 increase gradually between 14 and 20 wk gestational age and correlate with IGF-I and IGF-II levels; high IGFBP1 levels do not predict small for gestational age newborns, but are associated with lower placenta weight.     

Erythropoietin and hypoxia inducible factor-1 expression in the mid-trimester human fetus

Aim : Infants born prematurely lack a normal response to anemia and fail to increase erythropoietin (Epo) production despite an apparent need for improved tissue oxygenation. This anemia may involve a deficiency in the fetal and premature kidney to produce Epo. To evaluate fetal Epo production, Epo and hypoxia inducible factor-1 (HIF) mRNA expression was measured in the mid-trimester human fetus. Methods : Fetal liver and kidney samples were obtained at 11–22 wk of gestation. RNA was isolated and reverse transcribed from snap-frozen specimens. Epo and HIF cDNA concentrations were determined using real-time polymerase chain reaction (PRISM). Epo cDNA concentrations were standardized to HIF concentrations present in each sample. Results : HIF concentrations remained constant during gestation in kidney and liver samples. Epo cDNA concentrations in kidney did not change from 12 to 22 wk (8.4 ± 3.4 fg Epo pg⁻¹ HIF cDNA, 4.8 ± 1.4, 2.6 ± 0.4, and 4.2 ± 1.8 at 11–14, 15–16, 17–19, and 20–22 wk of gestation, respectively), while Epo cDNA concentrations in liver increased with gestation (74.5 ± 31.9 fg pg⁻¹ HIF, 23.8 ± 6.5, 96.4 ± 19.2 and 276.1 ± 28.5 at 12–14, 15–16, 17–19 and 20–22 wk of gestation, respectively, p ± 0.05, 20–22 wk of gestation liver samples vs all other gestations). Concentrations were 5–20-fold higher in liver than in kidney in each gestational group ( p ± 0.01, liver vs kidney).
Conclusion : HIF concentrations did not change with gestation in liver or kidney. The human fetal kidney produced approximately 5% of the total Epo mRNA measured during the second trimester. It remains to be determined how Epo production by these tissues is affected by premature birth.     

Circulating interleukin-1 receptor antagonist levels in neonates

Abstract Circulating interleukin-1 receptor antagonist (IL-1 Ra) levels have been shown to reflect disease activity in certain conditions in adults. We determined circulating IL-1Ra references values for healthy neonates (healthy preterms and term infants with mild disease only) on days 2 (n=17) and 4 of life (n=23). Mean gestational age was 35±2.6 weeks. On the 2nd day of life IL 1-Ra levels were 0.78 ng/ml (0.49/2.65), on day 4 0.38 ng/ml (0.20/0.48) (median, 25th/75th percentile,P=0.01). The values were not influenced by gender. In neonates with severe illness (septicaemia, asphyxia, neonatal respiratory distress syndrome), who received invasive intensive care, circulating IL-1Ra levels were significantly higher than in the reference group of healthy newborns. On the 2nd day of life 14.72 ng/ml (4.38/18.67) versus 0.78 ng/ml (0.49/2.65),P<0.0001; on day 4 of life, 3.38 ng/ml (0.80/11.99) versus 0.38 ng/ml (0.20/0.48),P<0.005 (values are median; 25th/75th percentile, Mann-Whitney U-Wilcoxon Rank Sum W Test, two-tailedP).Conclusion Compared to healthy individuals beyond the neonatal period, IL-1Ra concentrations are physiologically elevated within the first days of life and decline to low levels within days. In contrast, IL-1Ra levels are strikingly elevated in sick neonates.     

Influence of gestational age and intrauterine growth on leptin concentrations in venous cord blood of human newborns

BACKGROUND: The ob gene product leptin is involved in the regulation of body weight and energy expenditure, suggesting a potential role of leptin in embryonal and fetal development and progression of pregnancy. In term infants, leptin concentrations showed a positive correlation with birth weight. We aimed at comparing leptin cord blood levels in AGA (appropriate for gestational age) to SGA (small for gestational age) preterm and term newborns. PATIENTS AND METHODS: Ninety-seven human newborns, 47 females and 50 males, 33 born at term and 64 born before 36 weeks of gestation, were studied prospectively. Leptin concentrations in venous cord blood were determined using a specific RIA (radioimmunoassay). RESULTS: In term newborns, mean gestational age (GA) was 39 weeks (wk) (+/- 0.7 wk) and mean birth weight (BW) was 3316 g (+/- 473 g); in preterm newborns (n = 64), mean GA was 30 wk (+/- 5.0 wk) and mean BW was 1398 g (+/- 505 g). Mean standard deviation score of birth weight (BW SDS) was calculated as - 0.47. Mean leptin concentrations in term newborns differed significantly from those in preterm newborns (9.21 +/- 2.63 ng/ml vs. 1.58 +/- 0.88 ng/ml; p < 0.0001). In preterm and term infants, leptin concentrations showed a linear correlation with BW (r = 0.46; p < 0.0001) and GA (r = 0.48; p < 0.0001), respectively. Leptin levels were best predicted by an exponential regression model with GA (Leptin = exp(- 4.41 + 0.14 x GA); r = 0.61; p < 0.0001). Using multivariate regression analysis (r = 0.57; p < 0.0001), we found significant influences of GA (p < 0.00001) and BW SDS (p < 0.05) on leptin levels. No difference was observed between leptin values in AGA versus SGA preterm infants. CONCLUSION: These data suggest fetal leptin levels to be primarily determined by GA and additionally modulated by growth restriction in term newborns. We found a dramatic increase at weeks 33 to 35 of gestation and no modulation by BW SDS in very preterm infants.     

Effects of intrauterine growth restriction and intraamniotic insulin-like growth factor-I treatment on blood and amniotic fluid concentrations and on fetal gut uptake of amino acids in late-gestation ovine fetuses

OBJECTIVES: To investigate, in the late-gestation ovine fetus: 1) amino acid concentrations in blood and amniotic fluid, 2) the effects of intrauterine growth restriction (IUGR) induced by placental embolization on these concentrations, 3) fetal gut uptake of glutamine in healthy and IUGR fetuses, and 4) the effects of intraamniotic insulin-like growth factor-I (IGF-1) treatment on these parameters. METHODS: Fetuses were randomly assigned to control (n = 9), IUGR + saline (n = 9), or IUGR + IGF-1 (n = 11) groups. IUGR was induced by uteroplacental embolization from 114 to 119 days (term = 145 days). IUGR fetuses received daily intraamniotic injections of saline or IGF-1 (20 microg/d) from 120 to 130 days. RESULTS: Baseline amino acid concentration was higher in fetal blood than amniotic fluid for all essential amino acids except lysine and histidine, but was lower for serine, alanine, and methylhistidine. Embolization reduced total amino acid concentration in blood and amniotic fluid by approximately 15%. Concentrations were reduced for serine, glutamine, and methylhistidine in blood and for serine in amniotic fluid, but were increased for glycine, alanine, and asparagine in blood and for alanine in amniotic fluid. Glutamine was taken up by the fetal gut (glutamine:oxygen quotient of 0.65) and citrulline was released by the gut. IGF-1 treatment did not alter amino acid concentration in blood or amniotic fluid, but reduced gut uptake of glutamine from blood and the gut glutamine:oxygen quotient by 15%. Citrulline release was unchanged. CONCLUSIONS: These data suggest that amniotic fluid amino acids are not simply filtered from fetal blood and may provide an important pool of nutrients for the fetus. They demonstrate for the first time that glutamine is taken up by the fetal gut. IGF-1 treatment may promote gut utilization of amino acids from the amniotic fluid pool.     

Inter-relationship between serum concentrations of glucose, glucagon and insulin during the first two days of life in healthy newborns

The relationship between serum concentrations of glucose, insulin and glucagon during the first two days of life was studied in healthy newborns. The first capillary blood sample was obtained at 3–15 h of age (median 6h; day 0) and a second sample approximately 24 h later (day 1). Serum glucose concentrations in the first sample averaged 2.1 ± 0.07mmol/l (mean ± SEM; n = 60) and were positively correlated with postnatal age ( p < 0.01). Serum glucagon concentrations in the first sample averaged 570 ± 32pg/ml and were inversely correlated with glucose concentrations ( p < 0.0001). At the second sampling, serum glucose concentrations had increased to 2.9 ± 0.07mmol/l ( p < 0.001; n = 57) and serum glucagon concentrations had decreased to 403 ± 22pg/ml ( p < 0.001). Serum insulin concentrations were 11.7 f 0.3 μU/ml and 10.2 ± 0.3 μU/ml at the two samplings and did not correlate with serum glucose concentrations. The relationship of serum glucose and hormone concentrations to maternal and infant characteristics was studied by stepwise regression analysis. Serum glucose concentration on day 0 was positively correlated with postnatal age ( p < 0.01) and birth weight ( p 0.05) but inversely correlated with duration of labour ( p < 0.05). Serum glucose concentration on day 1 was positively correlated with birth weight ( p < 0.0001) and inversely correlated with maternal prep-pregnancy weight ( p < 0.05). Similar analyses of serum hormone concentrations did not demonstrate any relationships with maternal or infant characteristics. It is suggested that glucagon secretion is part of the counter-regulation against hypoglycaemia in healthy newborns and that neonatal energy stores, as indicated by birth weight, influence the ability to increase circulating glucose concentrations in response to counter-regulatory hormones.     

Thyroid hormone metabolism in amniotic and allantoic fluids of the sheep.

Amniotic and allantoic fluid samples were obtained at the time of uterotomy from healthy pregnant ewes at various time during gestation. In most instances maternal and fetal blood was collected simultaneously. Serum thyroxine (T4) and triiodithyronine (T3) and free T4 were measured in most samples. To determine whether conjugastes of T4 were presented in amniotic and allantoic fluids. T4 was measured before and after 24-hr acid hydrolysis. T4 and T3 turnover from amniotic fluid were measured using kinetic methods after intravenous or intraamniotic fluid injection of radiolabeled hormones. T3 was unmeasurable less than 15 ng/100 ml) in amniotic and allantoic fluids as well as in most fetal serum samples. T4 levels in amniotic fluids were low before 120 days of gestation (0.17 +/- 0.03 mug/100 ml; mean and SEM) concentration between 124 and 152 days was 0.33 +/- 0.03 mug/100 ml. T4 concentrations in allantoic fluid were relatively high before 120 days (0.57 +/- 0.1 mug/100 ml) and did not increase with progression of the pregnancy...     

Third trimester fetal growth and umbilical venous blood concentrations of IGF-1, IGFBP-1, and growth hormone at term.

Insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-1 (IGFBP-1) and growth hormone (GH) concentrations were measured in umbilical venous blood after delivery of 78 term newborn infants. Three groups of pregnancies were prospectively identified during the third trimester, according to fetal size and subsequent fetal growth, assessed by repeated ultrasound scans. Fetal size was considered either appropriate for gestational age (AGA) or small for gestational age (SGA), according to whether the first ultrasound measurement of abdominal circumference was equal to or above, or below the tenth centile for gestational age, respectively. Subsequent fetal growth was quantified by the change in the standard deviation score of abdominal circumference measurements between the first and last scans before delivery. Fetal growth retardation (FGR) was defined as a (negative) change in SD score of greater than -1.5. Eighteen SGA fetuses with evidence of FGR had significantly lower IGF-1 (median 0.05 (range 0.0-0.24) U/ml) at delivery than 35 SGA fetuses with normal growth (median 0.13 (range 0.0-0.94) U/ml; P < 0.05) and 25 AGA fetuses with normal growth (median 0.31 (range 0.0-0.84) U/ml; P < 0.05). The median concentration in the SGA group with normal growth was also significantly lower than that of the AGA group with normal growth. There were no significant differences in IGFBP-1 or GH concentrations between the three groups. These observations indicate that umbilical blood concentrations at birth of IGF-1, but not IGFBP-1 or GH, relate to both fetal size and fetal growth during the third trimester of pregnancies reaching term.     

Cord blood interleukin-10 levels are increased in preterm newborns

Cell-mediated immunosuppression due to interleukin (IL)-10 may contribute to normal pregnancy. By contrast, delivery is associated with a predominance of T-helper-1 (Th1) cytokines (IL-12, interferon-γ) and might be regarded as a graft rejection process. The aim of the study was to assess IL-10 and IL-12 levels in cord blood samples from newborns and their normal mothers in relation to the gestational age and type of delivery. Cord blood and serum samples were obtained from 31 term newborns (gestational age 38–42 weeks) and 40 preterm newborns (mean gestational age 32 weeks). Serum samples were obtained from 26 mothers of term newborns at birth. There were 18 term and preterm infants born by caesarean section. Measurements of IL-10 and IL-12 levels by ELISA were repeated in mothers 15 days after delivery and in 11 preterm infants (median 14 days of age). Cord blood IL-10 levels were significantly higher in preterm than in term newborns (median 17.0 versus 3.2 pg/ml, P = 0.0001), but were similar to term newborns and paired mothers (2.2 versus 1.0 pg/ml). Term and preterm newborns also showed similar cord blood IL-12 levels (median 349 versus 320 pg/ml), and these levels were significantly higher when compared to their paired mothers (median 14.5 pg/ml, P = 0.0003). Cord blood IL-10 levels showed a significant inverse correlation with gestational age (P = 0.0001). When preterm infants, at several weeks post-delivery, were compared to gestational age matched newborns, their IL-10 levels were similar (median 8.3 pg/ml) whereas IL-12 levels were clearly lower(147 pg/ml; P = 0.0007). The type of delivery (vaginal versus caesarean) did not influence cord blood IL-10 and IL-12 results. Conclusion Cord blood IL-10 levels are increased in preterm newborns and may be due to the immunosuppression occurring during pregnancy and to fetal immaturity because these levels are inversely correlated with gestational age. Received: 18 December 1998 and in revised form 12 October 1999 / Accepted: 25 October 1999     

Ontogeny of unconjugated estriol in fetal blood and the relation of estriol levels at birth to the development of respiratory distress syndrome

Unconjugated estriol (E3) was quantified in serum of umbilical cord blood of 533 newborn infants, 360 of whom were delivered between 23 and 37 wk of gestation. Serum E3 levels rose (F = 7.71, p less than 0.0001) as a function of gestational age; the mean concentration of E3 at 37.5-42 wk of gestation (105 ng/ml, n = 173) was significantly higher than that in serum of newborns delivered at 23-28 wk of gestation (63 ng/ml, n = 33). Umbilical cord serum levels of E3 were significantly higher among newborns delivered vaginally between 31.5 and 42 wk of gestation than among newborns delivered by cesarean section (p less than 0.005). Although serum E3 levels correlated highly (p less than 0.0001) to newborn weight throughout the entire period of gestation, there was no relationship of newborn weight to umbilical serum E3 levels within a given gestational period. Also, the umbilical serum levels of E3 in male infants were similar to those of female infants at each gestational age. Significant changes in umbilical serum levels of E3 as a function of gestational age were not observed among newborns (n = 90) who developed respiratory distress syndrome (RDS). The mean umbilical serum concentration of E3 in newborns delivered at 34.5-37 wk of gestation who developed RDS were significantly lower (p less than 0.01) than that in similar aged newborns whose lung function was normal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue and plasma somatomedin-C/insulin-like growth factor I concentrations in the human fetus during the first half of gestation

To investigate the possible role of somatomedin-C/insulin-like growth factor I (Sm-C/IGF I) in early human development, we measured this peptide by radioimmunoassay in extracts of multiple tissues and in plasma from fetuses during the first half of gestation (9-19 wk). All tissues contained Sm-C/IGF I far in excess of that which could be accounted for by Sm-C/IGF I derived from blood entrapment. Lung and intestine had the highest concentrations (166 +/- 35 mU/g, n = 25 and 160 +/- 20 mU/g, n = 19, respectively; mean +/- SEM) and liver the lowest (67 +/- 16 mU/g, n = 26). Plasma concentrations were 270 +/- 20 mU/ml (n = 20). Neither fetal weight (6-258 g) nor gestational age correlated with Sm-C/IGF I concentrations in any tissue or in plasma. These findings suggest that Sm-C/IGF I is synthesized in many human fetal tissues from as early as the 1st trimester. They also provide further evidence for an autocrine/paracrine role of this peptide growth factor.     

神经管缺陷胎儿和神经管缺陷胎鼠羊水蛋白质标记物的比较研究

目的 利用表面增强激光解析/离子化飞行时间质谱(SELDI-TOF-MS)技术研究神经管缺陷胎儿羊水和神经管缺陷胎鼠羊水的蛋白质谱变化规律.方法 根据实验对象不同分为①经超声确诊为胎儿神经管缺陷的孕妇11例为畸形组.包括脊柱裂5例,无脑儿5例.脑积水1例,病例组孕母均于引产前经腹抽取羊水5 ml,另选产前行羊膜腔穿刺取羊水做染色体核型检测,结果正常且孕周数相匹配的正常孕妇9例为对照组;②45只雌性Wistar大鼠(体重220～260 g),随机分为畸形组(n=30)和对照组(n=15).在标准条件下饲养,午夜雌:雄=4:16笼.次日清晨8时阴道涂片,镜检精子,确定其妊娠日期,有精子者计为孕0日(E_0).在孕10日(E_10)晨8时,畸形组雌鼠称体重.按120mg/kg称取维甲酸与矿物油混合均匀(维甲酸浓度为40mg/ml),经胃管一次注入孕鼠胃内.对照组仅将与畸形组同量且不含维甲酸的矿物油经胃管一次注入.在孕17 d剖腹,每只胎鼠抽取羊水约0.1～0.3 ml,选取11只脊柱裂畸形胎鼠的羊水,15只正常对照胎鼠的羊水.选用CM10蛋白质芯片,在PBSⅡ C型蛋白质芯片阅读机读取数据.采用Ciphergen protein chip 3.1.1软件对数据进行统计分析.结果在设定的优化相对分子量1～30 × 10~3范围内,神经管缺陷胎儿的孕母羊水中共检测到35个差异蛋白峰,其中7个有统计学意义,有6种蛋白质/多肽高表达,相对分子质量分别为14 700,7 995,15 891,16 027,13 776,11 040;1种蛋白质/多肽低表达,相对分子质量为23 417.神经管缺陷胎鼠羊水中共检测到55个羊水差异蛋白峰,有统计学意义的差异蛋白峰有9个.脊柱裂畸形组有5种蛋白质/多肽高表达,相对分子质量分别为11 658,27 387,7 898,11 603,13 829;4种蛋白质/多肽低表达,相对分子质量分别为5 124,14 702,5 403,13 626.将神经管缺陷胎鼠和神经管缺陷胎儿羊水蛋白质谱进行比较分析,发现二者羊水中共同蛋白质/多肽:4 138(4 145),7947(7941),8 588(8 588),9 385(9 390),14 702(14 700).其中14 700(P=0.006)差异具有统计学意义,很可能是神经管缺陷胎儿和神经管缺陷胎鼠羊水共同蛋白质/多肽标志物.结论 神经管缺陷胎儿和胎鼠羊水中可能存在相同的特异性蛋白质/多肽标志物,相对分子质量14 700的蛋白质/多肽对神经管缺陷诊断具有更重要的意义.