Endogenous tissue plasminogen activator in neonatal cerebrospinal fluid

Tissue type plasminogen activator (tPA) plays a role in differentiation of neurones and activity-dependent structural changes in neurones. We hypothesised that tPA would also be present in CSF during fibrinolysis after intraventricular haemorrhage. We measured tPA antigen in CSF from 13 normal newborn infants and 14 infants with posthaemorrhagic ventricular dilation (PHVD). tPA was undetectable or at the limit of detection (1 g/l) in normal CSF. The CSF tPA concentration ranged from 1.3 to 3.5 g/l in the infants with PHVD. Serial tapping in one infant showed persistence of tPA in the CSF from 3 to 8 weeks of age. We conclude that endogenous tPA may be part of the physiological response to intraventricular haemorrhage or may be present as a result of passive diffusion into the CSF.     

Macromolecular Absorption in Preterm and Term Infants

ABSTRACT. Human o-lactalbumin (α-LA) has been used as a marker for measuring macromolecular absorption. The serum concentration of human α-LA after a human milk feed has been studied in 32 healthy very low birthweight infants (VLBW), fed human milk (gestational age 26–32 weeks) and in 56 term, breast-fed infants, age 3–140 days. At 31 weeks of gestation the serum concentration of human α-LA was more than 10 times higher (mean value 3000 and median value 2101 μg/1 serum/1 human milk/kg body weight, n = 11) than in the term infants aged 3–30 days (mean value 257 and median value 152, n = 29). The serum concentration of o-LA decreased with increasing maturity in the VLBW-infants. At a postconceptional age of 37 weeks the values were similar (mean value 200 and median value 99, n = 8) to those found for term infants during the first month. In the term infants a decreasing absorption of α-LA was found with increasing postnatal age.     

PLASMA CONJUGATED CHOLIC ACID IN PREMATURE AND TERM NEWBORNS AND YOUNG INFANTS

ABSTRACT. Tikanoja, T., Tikanoja, S. and Simell, O. (Children's Hospital, University of Helsinki, Helsinki, Finland). Plasma conjugated cholic acid in premature and term newborns and young infants. Acta Paediatr Scand, 70:491,.–Bile acid handling by neonates, both premature (Group 1, mean gestational age 34.3 weeks; Croup II, 36,6 weeks) and full-term (Group HI, 40.2 weeks) and by 3-month-old infants (Group IV) was assessed by measuring plasma concentrations of conjugated cholic acid (CCA) before and at successive intervals after feeds. The prefeeding CCA concentrations were highest in Group I (log mean 8.2; range 1.8–28.6 μmol/1) and lower in Groups II (7.5; 2.6–22.4 umol/1), III (5.1; 2.1–11.1 μ0mol/1), and IV (2.2; 0.5–6.1 μmol/1). The mean postprandial increments correlated with maturity: the rises for Groups I-IV were 3.7, 4.3, 1.0 and 0.7 μmol/1, respectively. Peak values were consistently reached at 30 min after the start of the feed, i.e., strikingly earlier than in older children and adults. After the peaks the return to prefeeding levels occurred rapidly in Groups II-IV but more slowly in the most premature infants (Group I). The rapid postprandial rise may be due to many factors, e.g., passive jejunal absorption, immature hepatic-clearing mechanisms, or rapid transit of bile acids to the ileum. Hence, measurements of postprandial plasma bile acids would appear ill-suited for detection of disturbed ileal function in young infants. The high concentrations in healthy newborns suggest that caution is necessary in interpreting plasma bile acid concentrations during the first few weeks of life, especially in premature infants.     

Neonatal plasma vitamin K1 levels following oral and intramuscular administration of vitamin K1

Vitamin K₁ levels were measured by high performance liquid chromatography in cord blood ( n = 33) and at the age of 97–120 h after administration of 2 mg of vitamin K_l orally ( n = 88) or 1 mg of vitamin K₁ by im injection ( n = 88). Vitamin K₁ levels were less than 0.05 μg/l in cord blood. The mean (range), SEM, mode and median values (μg/l) for the infants given oral vitamin K₁ were 17.99 (1–56), 1.25, 8 and 15.5 and those for the infants given im vitamin K_l 15.83(2–57), 1.01, 11and 14, respectively. The t- test showed no significant difference in the mean values ( p = 0.09) in the infants given oral or im vitamin K.     

Serum creatinine and creatinine clearance in healthy neonates and prematures during the first 10 days of life

Normal serum creatinine (Scr) and creatinine clearance (Ccr) values during the first 10 days of life were obtained in 63 very premature (28–32 weeks of gestation), premature (33–37 weeks) and term infants (38–42 weeks). Scr fell, and Ccr rose less markedly in the very premature infants. Scr was 80 mol/l on the 1st day of life both in very premature and premature infants, and 77 mol/l in full-term neonates. After 10 days, Scr was 73, 53 and 35 mol/l respectively. There was an exponential correlation between Ccr and gestational age, indicating rapid maturation of glomerular function.Abbreviations Scr serum creatinine - Ccr creatinine clearance - GA gestational age - GFR glomerular filtration rate     

Endogenous nitric oxide in the upper airways of premature and term infants

Concentrations of endogenous nitric oxide (NO) were measured in premature ( n = 18) and term infants ( n = 7). Nasal gas was aspirated continuously and after timed occlusions, 15 s and 60 s, by a fast-response chemiluminescence analyser. The sampling flow rate was 20 ml min^-1. Typical NO recordings consisted of plateaux and postocclusive peaks. In term infants peak NO concentrations (60 s occlusion) were 2. 71 ± 0. 44 parts per million (ppm) within lOmin after birth, increasing ( p < 0. 05) to 3. 81 ± 0. 25 ppm at 4–7 d postnatally. Peak NO values (15 s occlusion) averaged 1. 22 ± 0. 16 ppm in premature infants (postconcep-tional age 25–37 weeks, body weight 623–2844 g) and the NO concentrations increased significantly with postconceptional age ( p < 0. 05). Nasal excretion rate, estimated from plateau NO concentrations and sampling flow rate, was 0. 10 ± 0. 01 nmol min^-1 kg^-1 in both groups. We conclude that premature and term newborn infants excrete considerable amounts of NO in the upper airways, with hitherto not fully known functions.     

SERUM CHOLESTEROL CONCENTRATIONS IN NEWBORN INFANTS WITH GESTATIONAL AGES OF 28–42 WEEKS

Abstract. Ginsburg, B.-E. and Zetterström, R. (Department of Paediatrics, Karolinska Institute, St. Göran's Children's Hospital, Stockholm, Sweden). Serum cholesterol concentrations in newborn infants with gestational ages of 28–42 weeks. Acta Paediatr Scand, 69: 587, 1980.—Serum total cholesterol, HDL-cholesterol and VLDL-LDL-cholesterol were determined in 53 newborn infants with gestational ages of 28–42 weeks. In pre-term infants (gestational age < 37 weeks) the total cholesterol concentration in cord blood was higher than in term infants. Mean values were 2.4 and 1.7 mmol/l, respectively. The HDL-cholesterol/ VLDL-LDL-cholesterol ratio was 1.8 in pre-term and term infants. In 11 pre-term and 17 term infants a second determination was made 3–4 days after birth. Total cholesterol had increased more in term than in pre-term infants and the difference found at birth had already levelled out. Mean value was 3.0 mmol/I in pre-term and term infants. The HDL-cholesterol/ VLDL-LDL-cholesterol ratio had changed to 0.6 in pre-term and term infants. Six pre-term infants who received intravenous fluids only were also studied. Their values did not differ from those in pre-term infants fed orally. Free and esteritied cholesterol were determined in 26 infants of varying gestational ages. About one-third of the total cholesterol was in the free form in pre-term and term infants at birth and during the first days of life.     

Vitamin A Nutrition in the Human Foetus: A Comparison of Sweden and Ethiopia

ABSTRACT. The accumulation of vitamin A during foetal development was investigated post mortem in foetuses and newborn infants of well-defined socio-economic groups of Swedish and Ethiopian women. The median vitamin A concentration in the liver was 37.0 μg/g in the Swedish foetuses (n=39) and 9.1 μg/g in the Ethiopian ones (n=49) (p<0.001). The liver vitamin A concentration in the Swedish foetuses increased exponentially during the second and third trimesters of pregnancy. This trend was not evident in the Ethiopian material. The mean serum concentration of retinol-binding protein was only slightly lower in the healthy Ethiopian newborns (18.6 mg/l; n=70.) than in the Swedish newborns. This finding suggests that vitamin A is retained i the foetal circulation in preference to storage, much like the situation in a vitamin A deficiency state in the adult.     

Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method

Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations.     

Morphine pharmacokinetics in premature and mature newborn infants

The pharmacokinetics of a single dose of morphine was investigated in five term infants (gestational age 37–40 weeks) and eight preterm infants (gestational age 25–32 weeks). In the five term infants, median (range) volume of distribution at steady state (Vd_β) was 1758 (634–2700) ml/kg, plasma clearance (Cl) was 4.73 (1–75–6.61) ml/kg/min and terminal half-life (T1/2) was 224 (107–394) min. In the eight preterm infants, Vd_β was 2366 (1662–2876) ml/kg, Cl was 2.82 (1.88–6.60) ml/kg/min and T1/2 was 556 (248–834) min. No correlation was found between clearance and gestational age, but we found a significant negative correlation between T1/2 and gestational age. We conclude that there is considerable variation in the pharmacokinetic properties of morphine in both term and preterm newborn infants. Because of this variation, careful individual assessment of the clinical effect of therapy with morphine in newborn infants should be exercised.     

TGF-β1 和PAI-1 在早产儿支气管肺发育不良中的表达及意义

目的 探讨支气管肺发育不良（BPD）与转化生长因子-1（TGF-β1）及纤溶酶原激活物抑制剂-1 （PAI-1）的关系。方法 回顾性分析2010 年1 月至2012 年12 月间胎龄≤ 32 周并存活28 d 以上极低出生体重儿96 例的临床资料,其中BPD 组21 例,非BPD 组75 例。采用ELISA 法测定2 组患儿血液中TGF-β1、PAI-1 的表达。结果 BPD 组TGF-β1 和PAI-1 在生后第7、14、21 天表达逐渐增高,且高于同时间点非BPD 组,差异有统计学意义（PP>0.05）。结论 BPD 组患儿血液中TGF-β1 及 PAI-1 表达增高,BPD 的发病过程可能与TGF-β1 及 PAI-1 高表达有关。     

Tissue-type plasminogen activator, plasminogen activator inhibitor, and histidine-rich glycoproteins in stressed human newborns.

Normal newborns have reduced levels of tissue-type plasminogen activator (tPA). Stressed newborns have an increased prevalence of thrombotic diseases. An impaired release of tPA and/or increased plasminogen activator inhibitor (PAI) is associated with thrombotic risk in the adult patient. The purpose of this study was to assay the plasma levels of tPA, PAI, histidine-rich glycoprotein (HRG), and other fibrinolytic proteins in 15 severely stressed newborns. The stressed babies showed significantly higher (p less than .001) levels of tPA antigen compared with normal newborns. Also, PAI activity and PAI-1 antigen levels were increased. Levels of both HRG and plasminogen were higher in the stressed group but the ratio of HRG to plasminogen was the same as that in the normal control newborns (1:3), suggesting an insignificant effect of HRG. D-dimers were significantly elevated in the stressed newborns. However, 8 patients died and 4 of these were found to have massive thrombotic disease on autopsy. These results show that the newborn when stressed will increase tPA levels and activate the lytic system. However, the activity is suboptimal inasmuch as PAI activity did not decrease and thrombotic disease was observed.     

Histidine-rich glycoprotein and plasminogen plasma levels in term and preterm newborns

The newborn's fibrinolytic system is not the same as that in the adult. Hypoplasminogenemia with normal (adult) levels of alpha 2-plasmin inhibitor and plasminogen activator inhibitor are characteristic of the newborn's lytic system. This combination suggests that the newborn may have an impaired lytic system that may explain, in part, the thrombotic events that are frequently observed. Histidine-rich glycoprotein (HRG), another fibrinolytic inhibitor, retards fibrinolysis by interfering with plasminogen's binding to fibrin. Levels of HRG have been reported to be reduced in term newborns. This finding has not been studied recently and to our knowledge, there are no reports of HRG levels in premature infants. The purpose of this study was to measure the plasma levels of HRG and plasminogen in three groups of patients: normal adults (n = 48), normal term newborns (n = 43), and normal premature newborns (n = 18). The protein levels were determined by electroimmunoassay. Cross-immunoelectrophoresis was also performed for HRG. Cord blood was employed for obtaining newborn citrated plasma. The newborns had significantly lower plasminogen and HRG levels when compared with those of the adults. Also, the HRG levels of the premature newborns were lower than those of the term newborns. In conclusion, the newborns had lower levels of HRG than adults, with premature newborns having the lowest levels. This may allow for more plasminogen to be available for fibrin binding even though newborns have hypoplasminogenemia.     

Protein C Activity and Antigen in Premature and Fullterm Newborn Infants

ABSTRACT. Blood was obtained from 23 premature infants (birthweights 950–2910 g at 26–35 gestational weeks), and 27 fullterm infants (birthweights 2930–4900 g at 37–42 gestational weeks). Protein C concentration and activity were analysed. In preterm infants, protein C concentrations were 2.9–24% of adult values, and those of protein C activity 6–32%, the corresponding figures for term infants being 16–60% and 8.5–60%. Protein C concentrations were below 10% of adult values in four low birthweight infants, three of whom had significant haemorrhages. Protein C activity was below 10% of adult values in three infants, all of whom suffered from major haemorrhages.     

定量超声技术对婴儿出生时骨状况的研究

目的　评价定量超声(QUS)技术在新生儿中的应用,取得新生儿出生时骨QUS的基础资料。方法　采用以色列Sunlight公司生产的Omnisense定量超声仪,对 157例新生儿进行出生时胫骨声波速度(SOS)测量。结果　 ①男女婴儿之间SOS值差异无统计学意义 (男 88例,SOS值为2968±115m/s;女 69例,SOS值为 2956±105m/s;P=0. 524)。早产儿 (68例,平均胎龄 33 0±2. 5周)SOS值平均为 2935±96m/s,足月儿(89例, 平均胎龄 39. 4±1 3周)SOS值平均为 2984±116m/s,早产儿SOS值显著低于足月儿 (t=2 837,P=0. 005)。②不同季节出生的新生儿其SOS值差异有统计学意义(F=4.377,P=0 005);新生儿SOS值在春夏季出生者显著低于秋冬季出生者,夏季出生者比冬季出生者低 2 3%。③出生体重<1500g新生儿SOS值 (11例,SOS值为 2908±99m/s)显著低于出生体重>2500g新生儿(86例,SOS值为 2980±113m/s) (P=0 .042)。④在 109例适于胎龄儿中,SOS值与胎龄显著相关(r=0.270,P=0 .005),与出生体重也显著相关 (r=0. 232,P=0 015),多元回归分析发现胎龄和出生季节是影响SOS值的重要因素 (F=8 515.P<0. 001,校正决定系数R2 =0. 141)。结论　QUS适用于新生儿骨状况的研究;本研究取得了新生儿出生时骨SOS值的资料。     

Postnatal changes in blood spot 17-hydroxyprogesterone level in healthy preterm and full-term neonates

Blood spot 17OH-P concentrations were determined in 14 healthy premature (mean birthweight 1439 g, mean gestational age 30 weeks) and full-term newborn infants (mean birthweight 3532 g, mean gestational age 39.2 weeks) during the first five weeks of life to provide reference data for infants with various gestational and postnatal ages. It was demonstrated that with advancing age there was an abrupt fall in 17OH-P from 296.2 +/- 84.1 nmol/l on the first day to 101.2 +/- 19.5 nmol/l on the 7th day (p less than 0.001) and 75.7 +/- 8.7 nmol/l (p less than 0.05) on the 14th day in premature infants. In full-term neonates its initial value is much lower (90.1 +/- 12.5 nmol/l) and its fall during the first week is much less pronounced (51.5 +/- 6.5 nmol/l, p less than 0.01). Comparing the postnatal changes in 17OH-P in the two groups it proved to be significantly higher in premature than in full-term infants at all ages except for the 4th week. When blood spot 17OH-P values were studied as a function of gestational age at the age of 5 days a significant inverse relationship was found between the two parameters. It is assumed that in addition to placental 17OH-P production and perinatal stress, renal salt wasting may also account for the long lasting elevation of 17OH-P plasma level seen in premature infants.     

Erythrocyte indicators of oxidative stress in gestational diabetes

Foetuses born to mothers with gestational diabetes are at increased risk of developing respiratory distress, foetal macrosomia, foetal anomalies and platelet hyperaggregability. High blood glucose level induces oxidative stress and decreases antioxidant defences. The present study discusses the possibility of lipid peroxidation and protein oxidation in both maternal and foetal erythrocytes as an indicator of oxygen radical activity. The level of lipid peroxidation and protein oxidation in erythrocytes was estimated in 20 mothers with gestational diabetes and their newborns. The maternal age varied between 19 and 42 y and foetal age ranged between 34 and 39 weeks. The proteolytic activities in the erythrocyte lysates obtained from mothers with gestational diabetes and their newborns were significantly greater [(mean ± SD) 24.41 ± 9.05 and 16.70 ± 3.36μM of amino groups/g haemoglobin, n = 20, respectively] than those from control group (10.18 ± 4.84 and 14.64 ± 6.21 μM amino groups/g haemoglobin, n = 15, respectively; p < 0:05 in both cases). Similarly erythrocyte malondialdehyde levels were significantly elevated in babies born to mothers with gestational diabetes (10.11 ±2.21 nM/g haemoglobin) when compared to controls (6.8 ± 3.75 nM/g haemoglobin) (p < 0:05). In the erythrocytes of mothers with gestational diabetes, malondialdehyde levels correlated significantly with glycated haemoglobin levels (p < 0:01). The results of this study indicate that the oxidative stress induced by gestational diabetes manifests as increased lipid peroxidation and protein oxidative damage in the erythrocytes of both mothers with gestational diabetes and their newborn infants.     

Macromolecular Absorption in Infants with Infantile Colic

ABSTRACT. Intestinal absorption of macromolecules, using human α-lactalbumin (α-LA) as a marker, was studied in breast-fed and formula-fed infants with infantile colic. Serum samples taken at 30 and 60 min after an intake of human milk were analyzed for α-LA by a competitive radioimmunoassay technique. Breast-fed infants with infantile colic had significantly higher s-α-LA levels compared with age-matched breast-fed control infants 0-1 month of age: median value 926 μg α-LA/I serum/I human milk/kg bodyweight (n= 11) versus 150 (n= 34); 1–2 months of age: 173 (n= 22) versus 31 (n= 16); 2–3 months of age: 132 (n= 8) versus 11 (n= 16). Similarly, formula-fed colicky infants had significantly higher s-α-LA levels than agematched formula-fed control infants 1-2 months of age: median value 126 (n= 12) versus < 10 (n= 14); 2–3 months of age: 156 (n= 11) versus < 10 (n= 10). The increased absorption of the macromolecule human α-lactalbumin in infantile colic suggests that the gut mucosa is affected in infants with infantile colic.     

早产母乳营养成分的分析

目的 探讨早产儿母亲乳汁营养成分的特点及动态变化。方法 收集2012 年11 月至2014 年1月在北京协和医院产科分娩产妇170 人的母乳339 份,用MIRIS 母乳分析仪检测母乳中宏量营养素及能量,比较各组母乳营养成分的差异。结果 （1）早产母乳中蛋白质含量：初乳> 过渡乳> 成熟乳（2.22±0.49 g/dL vs1.83±0.39 g/dL vs 1.40±0.28 g/dL;PPPPP+1~33+6 周组（2.11±0.25 g/dL）和≥ 34 周组（2.22±0.39 g/dL）比较差异有统计学意义（P+1~33+6 周（51±6 kcal/dL vs 58±8 kcal/dL,P+1~33+6 周组和≥ 34 周组（P+1~33+6 周成熟乳蛋白质显著高于≤ 30 周和≥ 34 周组（P结论 （1）早产初乳、过渡乳和成熟乳营养成分差异显著;（2）早产初乳蛋白质显著高于足月初乳,这种差异未能持续到成熟乳阶段;（3）不同孕周早产产妇母乳营养成分亦存在差异,以适应不同胎龄早产儿的营养需要。     

CYSTINE: A SEMI-ESSENTIAL AMINO ACID IN THE NEWBORN INFANT

ABSTRACT. Pohlandt, F. (Department of Paediatrics, Section of Neonatology, University Hospital, Ulm, Federal Republic Germany). Cystine: a semi-essential amino acid in the newborn infant. Acta Paediatr Scand 63: 801, 1974.—The enzyme activities of the transsulfuration pathway (Cystine biosynthesis) are low or not measurable in the livers of human fetuses, premature and full-term newborns. Cystine thus may be an essential amino acid in newborn infants. To test this suggestion, we studied the plasma amino acid concentrations in 20 premature and 7 full-term infants treated for prematurity and/or respiratory distress syndrome by ion exchange columnchromatography. The infants received infusions of a 5% glucose-electrolyte-solution during the first two days of life. In premature newborns the plasma cystine concentrations markedly decreased within the first 12 hours of life (median <5 μmol/l) and remained low tlfereafter. In full-term infants the plasma cystine concentrations decreased similarly. To rule out the possibility that these low plasma cystine concentrations were the result of a reduced cystine biosynthesis due to a lack of methionine, a substrate of transsulfuration pathway, we studied premature on infusion of a mixture of synthetic l -amino acids free from cystine. Despite elevated plasma methionine concentrations (median 113.4 μnol/l) the plasma cystine concentrations remained very low. Cystine, therefore, can be considered a semi-essential amino acid in the newborn infant and should be supplied to newborns receiving balanced parenteral nutrition.