新生儿凝血指标及部分生化指标检测参考区间调查

目的:调查分析新生儿凝血指标及部分生化指标检测参考区间。方法:以十所三甲医院2012年1月~2014年6月收治的新生儿2683例为研究对象,其中足月儿1700例,早产儿983例,选择同期十所医院职工健康体检1000例为对照组,通过全自动血凝仪、全自动生化分析仪测定所有对象凝血指标及12项生化指标,并建立相关指标参考区间。结果:足月新生儿PT、TT、APTT凝血指标较对照组延长,Fib较对照组降低,差异均有统计学意义(P=0.000);早产儿PT、TT、APTT较足月儿延长(P=0.000),Fib(P=0.001)降低;足月新生儿Glc水平较对照组低(P=0.000),早产儿Glc水平较足月新生儿更低(P=0.000);足月新生儿血钙水平低于对照组,血清TC、Cr、BUN、ALT含量均在对照组之下(P=0.000),早产儿相对更低(P均0.05);足月新生儿LDH、CK酶活性及K+水平均高于对照组(P均0.05),早产儿水平更高(P0.05);足月儿血清Alb、TP及Na+水平低于对照组(P0.05),早产儿更低(P均0.05)。结论:新生儿凝血表达与成人不同,凝血及部分生化指标参考区间的变化与年龄有联系,有必要为新生儿建立与年龄相关的凝血、生化指标参考区间。     

Latent anaphylactic sensitisation of infants of low birth weight to cows' milk proteins.

Latent systemic anaphylactic sensitisation to cows'' milk was assessed in 61 preterm infants who were randomly assigned to receive either a special formula for preterm infants based on cows'' milk or banked breast milk or one or other of these as a supplement to maternal milk. A single sample of venous blood was taken near to the time of discharge from the neonatal intensive care unit, and the histamine release by blood basophils in response to in vitro challenge with cows'' milk and anti-IgE was measured. Compared with the blood from infants fed on human milk, that from infants fed on preterm formula showed a significant increase in histamine release to challenge with cows'' milk, the response being greater in blood from infants of lower birth weight and gestational age. A smaller but significant increase in blood histamine release with anti-IgE challenge was observed in the group fed on preterm formula. Infants of low birth weight fed on preterm formula based on cows'' milk may develop latent systemic sensitisation more rapidly than infants born at term. The clinical importance of this requires further investigation.     

不同胎龄早产儿早期凝血指标的变化及其临床意义

目的:研究不同胎龄早产儿早期凝血指标的变化及其临床意义。方法:选取2012年1月至2017年7月期间我院出生的新生儿392例为研究对象。根据新生儿胎龄的不同分为早期早产儿组(胎龄27~31周)78例、中期早产儿组(胎龄32~33周)102例、晚期早产儿组(胎龄34~36周)116例以及足月新生儿组(胎龄37~42周)96例。四组新生儿出生后2h内抽取静脉血检测凝血指标,包括凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、纤维蛋白原(FIB),并应用Pearson相关性分析分析新生儿胎龄与上述各项凝血指标水平的相关性。结果:早期早产儿组、中期早产儿组、晚期早产儿组、足月新生儿组的出生体重以及胎龄呈逐渐上升趋势,不同组别新生儿的出生体重以及胎龄差异均有统计学意义(P0.05)。早期早产儿组、中期早产儿组、晚期早产儿组、足月新生儿组PT、APTT均呈逐渐下降趋势,FIB呈逐渐上升趋势,不同组别新生儿PT、APTT、FIB差异均有统计学意义(P0.05)。Pearson相关性分析显示,新生儿胎龄与PT、APTT呈负相关(r=-0.567、-0.691,P=0.000、0.000),而新生儿胎龄与FIB水平呈正相关(r=0.623,P=0.000)。结论:不同胎龄早产儿早期凝血功能存在异常变化,新生儿胎龄与PT、APTT均呈负相关关系,与FIB呈正相关关系,临床应予以重视,及时检测其凝血指标,必要时应予以干预治疗。     

Patterns of low birth weight in the Bengali newborns

This paper examines the distribution of low birth weight (2500 g or less) by gestation time, sex, maternal age, parity (birth order), socioeconomic conditions, and season of birth among 5117 single live births born to Bengali mothers at the Ramakrishna Mission Seva Pratisthan Hospital in Calcutta, India. Preterm infants have low birth weight significantly more often than their full term counterparts. Female infants have low birth weights significantly more often than male infants. The infants of poor mothers have lower birth weights in higher order births more often than infants of higher orders born to well-off mothers. Teenaged mothers produce low birth weight babies significantly more often than older mothers. Although the relationship is not significant, low birth weight infants occur more often among 1st and late born infants and less often among 2nd born infants. The season of birth is not significantly associated with birth weight. Less than 10% of low birth weight infants are pre-term, while the rest are full term. The great majority of low birth weight infants are small-for-gestational-age; the minority are small due to curtailed gestational age. The proportion of infants weighing less than 2001 g is only 9%; this figure tallies closely with earlier studies of India.     

Reduced survival of neonates due to vitamin A deficiency during pregnancy in the guinea pig

Neonatal vitamin A stores are limited even in well-nourished full-term infants and are yet smaller in the premature infant. The object of this experiment was to determine whether vitamin A deficiency could be induced in pregnant guinea pigs and, if so, whether it would affect vitamin A status of the neonate. Adult (600 g) guinea pigs were fed a casein-agar diet that was vitamin A deficient (AD). Controls (vitamin A adequate) were orally dosed weekly with 2 mg of retinyl palmitate. Weight gains of dams and birth weights of neonates did not differ. No external signs of deficiency were observed. Six of eight AD and seven of eight vitamin A-adequate dams carried pregnancy to term (greater than or equal to Day 64). One AD dam died during delivery. Liver retinol concentrations were below the detection limit (less than 3 micrograms/g) for all AD neonates and dams and in postpartum serum of AD dams. Of neonates born greater than or equal to Day 64, 15 of 18 AD were dead or moribund compared with 4 of 22 vitamin A adequate. The unexpectedly severe effect on the neonate indicates that the guinea pig will be a sensitive model for investigating the affect of poor maternal vitamin A status on neonatal vitamin A-dependent functions. However, a less severe maternal deprivation should be used for such studies.     

Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ

Background

Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants.

Methodology/Principal Findings

We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Gram-positive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-γ. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-γ.

Conclusion/Significance

Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressively matures in the last three months in utero. Ex vivo treatment of leukocytes from premature neonates with interferon-γ reversed their innate immune responses deficiency to bacteria. These data represent a promising proof-of-concept to treat premature newborns at the time of delivery with pharmacological agents aimed at maturing innate immune responses in order to prevent neonatal sepsis.     

Maternal and neonatal factors influencing premature birth and low birth weight in Australia

This study identified the influences of neonatal and maternal factors on premature birth and low birth weight in New South Wales, Australia. Bivariate and multivariate analyses were used to explore the association of selected neonatal and maternal characteristics with premature birth and low birth weight. The findings of this study showed that premature birth and low birth weight rate significantly varied by infant sex, maternal age, marital status, Aboriginality, parity, maternal smoking behaviour during pregnancy and maternal hypertension. First-born infants, and infants born to mothers aged less than 20 years, or who were single, separated/divorced, Aboriginal or who smoked during the pregnancy, were at increased risk of being premature or of low birth weight. This study also found that risk factors for premature births and low birth weight were similar in both singleton and multiple births. Gestational age was confirmed to be the single most important risk factor for low birth weight. The findings of this study suggest that in order to reduce the incidence of low birth weight and premature births, health improvement strategies should focus on anti-smoking campaigns during pregnancy and other healthcare programmes targeted at the socially disadvantaged populations identified in the study.     

Psychosocial stress in pregnancy and its relation to low birth weight.

The relation of low birth weight to psychosocial stress in pregnancy was examined using a life events inventory and a state anxiety index. Two hundred and fifty women were randomly selected and interviewed three times during pregnancy and shortly after delivery. Twenty six were excluded. Of the remaining 224 women, nine miscarried, 195 had healthy term babies, and 20 gave birth to babies that were either premature or of low birth weight at term. Low birth weight and prematurity were significantly associated with objective major life events but not state anxiety. The occurrence of objective major life events in the third trimester may be important in precipitating preterm labour. Cigarette smoking was the best predictor and objective major life events the second best predictor of low birth weight. The result was not dependent on social class. These findings suggest that cigarette smoking may be an important mediator of stress on the fetus. Antenatal care should take greater account of stress in pregnancy, and social support systems should be evaluated.     

Cord blood glutathione depletion in preterm infants: correlation with maternal cysteine depletion

Background

Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants.

Objective

Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH.

Methodology

Sixteen mothers delivering very low birth weight infants (VLBW), and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry.

Principal Findings

Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants.

Conclusion

The current data demonstrate that: 1) GSH depletion is present at the time of birth in VLBW infants; 2) As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates.     

Identification of infants destined to die unexpectedly during infancy: evaluation of predictive importance of prolonged apnoea and disorders of cardiac rhythm or conduction.

Twenty four hour tape recordings of electrocardiogram and breathing movement were made prospectively in 6914 full term and 2337 preterm infants or infants of low birth weight during their first six weeks of life. These recordings included 40 obtained in 29 infants who subsequently suffered the sudden infant death syndrome and 13 obtained in 10 other infants who died suddenly and unexpectedly. None of the recordings obtained in the infants who suffered the sudden infant death syndrome showed prolonged apnoea (cessation of breathing movement for 20 seconds or more) or pre-excitation. One infant had multiple ventricular premature beats (38/hour). Compared with recordings obtained in 211 control infants who did not die none of the recordings obtained in the infants who suffered the syndrome showed abnormal prolongation of the QT interval.     

深度水解蛋白配方奶在不同体重早产儿喂养中的临床效果观察

目的:评估深度水解配方奶(eHPF)在不同体重早产儿早期喂养中临床应用效果。方法:选取2017年9月至2018年12月出生的早产儿,分为极低出生体重儿组(体重1000-1500g之间)62例和低出生体重儿(体重1500-2000g之间)100例,每组再随机分为两组,分别予以深度水解蛋白奶(eHPF)和早产儿配方奶(SPF)喂养。极低出生体重儿组于12小时后开始微量喂养,低出生体重儿12小时内适量喂养;极低出生体重儿组深度水解蛋白奶喂养2周后改早产儿奶喂养,低出生体重儿组深度水解蛋白奶1周后改早产儿奶喂养。比较深度水解蛋白奶在不同体重早产儿早期喂养中的临床应用效果,不同体重早产儿恢复出生体重时间、每日体重增长速度、胃管留置时间、完全肠内喂养天数、住院天数、喂养不耐受发生率、宫外发育迟缓发生率及尿素氮、碱性磷酸酶指标。结果:深度水解蛋白喂养组极低出生体重儿/低出生体重儿恢复出生体重天数、完全肠道喂养天数、胃管留置时间、住院天数较早产儿奶喂养组明显缩短(P0.05),每天体重增长优于早产儿组,喂养不耐受、宫外发育迟缓发生率明显低于早产儿组(P0.05),尿素氮、碱性磷酸酶无统计学差异(P0.05)。结论:深度水解蛋白奶用于不同体重早产儿早期喂养效果明显优于早产儿配方奶,其更有助于早产儿的生长发育。     

Coagulation factor mutations and thrombosis

The coagulation system is governed by a subtle balance between clotting activators and inhibitors. Many genes can contribute to the overall phenotype, and polymorphisms may act to up regulate or down regulate the generation of thrombin, the coagulation-key enzyme. An increase in coagulation factor (gain function) or/and a decrease in coagulation inhibitors (loss of function) may favor venous thromboembolism (VTE). It has been observed since a long time that VTE may be a familial disease, but it was only in 1965 that Egeberg published the first case of inherited antithrombin (AT) deficiency. This was followed by similar reports of protein C (PC) and protein S (PS) deficiencies. Hereditary thrombophilia was thus initially considered as a rare monogenic disorder with incomplete penetrance. AT, PC and PS deficiencies are due to multiple and mostly private mutations of the corresponding genes. Most patients are heterozygous and experience VTE at adult age. Homozygosity associated with severe thrombosis at birth has been observed in newborns with undetectable PC or PS concentrations. The discovery of factor (F) V Leiden and F2 g.20210 G>A, two gain of function mutations, challenged the view of thrombophilia as a rare monogenic disorder. FV Leiden and F2 g.20210 G>A are due to a founder effect and affect populations of European descent with frequencies at 5% and 3% respectively. These two mutations are moderate of risk factor for thrombosis and paved the way for gene-gene and gene-environment interactions. Patients carrying more than one genetic risk factor are at higher risk to develop VTE. The exposition to acquired risk factors such as estrogen based oral contraception may also have a synergistic effect favoring thrombosis in patients with FV Leiden or other genetic risk factors.     

早产病因及发病机制的研究现状

早产在妇产科临床上比较常见,其作为围生医学当中的一类重要而复杂的妊娠并发症,对早产儿的预后具有较大危害,严重时可能直接导致早产儿死亡。通常而言,早产患者的临床表现主要是子宫收缩,初期表现为不规律的宫缩,并伴有少量的阴道出血亦或是血性分泌物,进而发展成规律性的宫缩,此过程中宫颈管先发生消退,而后扩张。早产儿的体重大多数低于2500 g,且头围小于33 cm,部分胎儿的器官功能及适应能力与足月儿相比明显较差,常需给予特殊的处理。因此,及时梳理导致早产的原因并分析其发病机制,有利于早期掌握防治早产的基础要点。本文就此展开综述,以期为改善母婴妊娠结局提供理论支持。     

Prematurity--another example of perinatal metabolic programming?

Low birth weight is associated with both later adult diseases such as type 2 diabetes mellitus and a number of metabolic abnormalities, the foremost of which is insulin resistance. Indeed the link between an adverse perinatal environment, manifested by low birth weight, and adult life pathology may be an early, permanent reduction in insulin sensitivity. A reduction in insulin sensitivity has been demonstrated in small for gestational age (SGA), term subjects from childhood through to adulthood. Less is known about children born premature into an adverse neonatal environment. We present data demonstrating that premature infants also have metabolic abnormalities similar to those observed in term, SGA children and that these occur irrespective of whether they are SGA or appropriate for gestational age (AGA).     

Time Course Study of Blood Pressure in Term and Preterm Infants Immediately after Birth

Objective

To describe temporal changes in systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP, respectively) in term and preterm infants immediately after birth.

Methods

Prospective observational two-center study. In term infants SBP, DBP, and MBP were assessed non-invasively every minute for the first 15 minutes, and in preterm infants every minute for the first 15 minutes, as well as at 20, 25, 30, 45, and 60 minutes after birth. Regression analyses were performed by gender and respiratory support in all neonates; and by mode of delivery, cord clamping time, and development of ultrasound-detected brain injury in preterm neonates.

Results

Term infants (n = 54) had a mean (SD) birth weight of 3298 (442) g and gestational age of 38 (1) weeks, and preterm infants (n = 94) weighed 1340 (672) g and were 30 (3) weeks gestation. Term infants’ SBP, DBP and MBP within the first 15 minutes after birth were independent of gender or respiratory support. Linear mixed regression analysis showed that preterm infants, who were female, born vaginally, had delayed cord clamping and did not require positive pressure ventilation nor develop periventricular injury or ventriculomegaly, had significantly higher SBP, DBP, and MBP at some measurement points within the first hour after birth.

Conclusions

We present novel reference ranges of BP immediately after birth in a cohort of term and preterm neonates. They may aid in optimization of cardiovascular support during early transition at all gestations.     

Photodegradation of riboflavin in neonates

The biologically most important flavins are riboflavin and its related nucleotides, all highly sensitive to light. It is because of its photoreactivity and its presence in almost all body fluids and tissues that riboflavin assumes importance in phototherapy of neonatal jaundice. The absorption maxima of both bilirubin and riboflavin in the body are nearly identical: 445-450 (447) nm. In consequence, blue visible light will cause photoisomerization of bilirubin accompanied by photodegradation of riboflavin. This results in diminished erythrocyte glutathione reductase, which indicates generalized tissue riboflavin deficiency and red cell lysis. Single- and double-strand breaks in intracellular DNA have occurred with phototherapy. This light exposure of neonates may result also in alterations of bilirubin-albumin binding in the presence of both riboflavin and theophylline (the latter frequently given to prevent neonatal apnea). Many newborns, especially if premature, have low stores of riboflavin at birth. The absorptive capacity of premature infants for enteral riboflavin is likewise reduced. Consequently, inherently low stores and low intake of riboflavin plus phototherapy for neonatal jaundice will cause a deficiency of riboflavin at a critical period for the newborn. Supplementation to those infants most likely to develop riboflavin deficiency is useful, but dosage, time, and mode of administration to infants undergoing phototherapy must be carefully adjusted to avoid unwanted side effects.     

301例早产儿视网膜病变筛查结果及其高危因素分析

目的:调查早产儿视网膜病变(ROP)的发生情况并分析其高危因素。方法:选取2017年6月至2018年6月在我院进行眼底检查的301例早产儿,依据《早产儿治疗用氧和视网膜病变防治指南》和《中国早产儿视网膜病变筛查指南》对早产儿进行筛查和随诊,同时收集早产儿及其母亲的相应病历信息,采用多因素Logistic回归分析分析ROP的高危因素。结果:301例早产儿中,共检出ROP患儿43例,其中须接受治疗的患儿13例,所有患儿经过2-6个月的治疗和随诊后均好转。围产因素中,胎龄小、出生体重低、吸氧、输血、有急性呼吸窘迫综合征(ARDS)的早产儿ROP检出率更高(均P0.05);母体因素中,多胎分娩的早产儿ROP检出率高于单胎分娩的早产儿(P0.05)。Logistic回归分析显示,胎龄小、出生体重低、吸氧、输血和有ARDS为早产儿ROP的高危因素(P0.05)。结论:早产儿ROP发病率较高,胎龄小、出生体重低、吸氧、输血和有ARDS是其高危因素,在临床实践中应给予重视,及早发现ROP并规范治疗,以降低早产儿ROP的发病率。