Oxidative stress in very low birth weight infants as measured by urinary 8-OHdG

Very low birth weight (VLBW) infants can be subjected to oxidative stress in the course of intensive care. We measured 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative stress, and estimated the degree of oxidative stress in such infants. We also examined if the administered oxygen was related to oxidative stress. Urine samples of 50 Japanese VLBW infants [birth weights: 956.3+/-277.6g, and gestational ages: 28.0+/-2.6 weeks (mean +/- SD)] were collected on various postnatal days and 8-OHdG levels were determined using an ELISA kit. Sixteen term infants served as normal controls. As body weights at sampling increased, the average levels of urinary 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants under 1000g, 29.5+/-16.4 micromol/mol creatinine (n = 24); 1000-1500g, 23.8+/-14.9 (n = 12); over 1500g, 16.1+/-8.5 (n = 14); and control, 10.9+/-7.2 (n = 16). Significant differences were found between <1000g group and > or = 1500g group (p = 0.0030), <1000g group and control (p < 0.0001), and 1000-1500g group and control (p = 0.0108). Also as postconceptional age at sampling increased, the average levels of 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants before 252 days (36 weeks) of postconception: 27.4+/-15.5 micromol/mol creatinine (n = 34); after 252 days, 18.2+/-12.5 (n = 16). Differences between <252 days group and control (p < 0.0001), and <252 days group and > or = 252 days groups (p = 0.0253) were statistically significant. Among the three groups based on ambient oxygen concentration (21%, 22-29%, and > or = 30%) there was no significant difference (p = 0.417). The more premature the infants were, the more intense was the oxidative stress, hence, it is the prematurity rather than the administered oxygen which causes oxidative stress in VLBW infants. Drury et al. ["Urinary 8-hydroxydeoxyguanosine in infants and children" Free Radic. Res. 28 (1998) 423-4281 measured urinary 8-OHdG of 28 infants (24-40 weeks gestation) and found no gestation or birthweight related differences. This discrepancy seemed to be because of difference in birth weights and sampling period of the subjects.     

Energy intake and the nature of growth in low birth weight infants

Growth is accompanied by and depends on energy storage in growing tissue. The rate of energy storage in growing low birth weight infants depends on the rate of energy intake and on the rates of energy excretion and expenditure, both of which (on a body weight basis) are much higher than in adults, and both of which increase with increments of gross energy intake. Energy-balance studies of growing low birth weight infants on gross energy intakes approximating 500 kJ X kg-1 X d-1 of mothers' milk or of infant formula indicate that the composition of extrauterine weight gain of the low birth weight infant differs from that of the fetus of similar gestation, in that the energy storage cost of growth is much higher. Attempts to increase metabolizable energy intake beyond 500 kJ X kg-1 X d-1 by energy supplementation alone do not result in proportionately increased rates of weight gain; low birth weight formulae, in which energy, protein, and mineral contents are all increased can result in large weight gains with proportionate increases in rates of protein and fat accretion.     

Retrolental fibroplasia; blindness in infants of low weight at birth

Retrolental fibroplasia is today the principal cause of blindness in children of preschool age, exceeding all other causes combined. The disease occurs in infants of low weight at birth, commonly those born prematurely. The incidence of the disease is rising at an alarming rate. Vitamin E deficiency, corticotropin (ACTH) deficiency, the use of cow's milk in place of mother's milk, and improper oxygenation have been suggested as etiologic factors but the cause remains a mystery. Often the incidence is high in institutions in which maximal care is given premature infants.Clinically, the disease advances through an "active" phase during which regression is possible, and a "subsiding" or "cicatricial" phase which terminates with the formation of a disorganized opaque mass behind the lens. The earliest manifestations are noted in the fundi. Hemorrhages, neovascularization, transudation commencing in the periphery, and retinal separation contribute to the formation of the characteristic retrolental membrane. The diagnosis may be made when the retrolental membrane is observed in the eye of an infant whose weight at birth was low. Differential diagnosis is required occasionally. Thus far, no form of therapy has prevented or reversed the pathologic changes successfully. Use of vitamin E, corticotropin and mother's milk has not influenced the incidence of the disease. Avoidance of premature delivery if possible is indicated.     

Risk factors of complicated postnatal period in low birth weight infants

Antropometric indices have been studied in 952 newborns. It has been shown those children with middle mass and height indices in birth have the most expressed homeostatic resources. Children with low body mass in birth are characterized by the decreasing of resistance and high morbidity. Phenotype B, incompatibility with mother according to ABO, Rhesus systems are the risk factors of complicated neonatal period course that results from the disturbances in balance of regulatory lymphocyte subpopulations.     

Effect of birthplace on infants with low birth weight.

From December 1983 to June 1985, 162 infants of less than 32 weeks'' gestation or weighing less than 1,500 g, or both, were cared for at the regional neonatal intensive care unit in Leeds. Of the 162, 64 (40%) were born in the unit because their mothers had received antenatal care there, 58 (36%) were born in another hospital and subsequently transferred, and 40 (25%) were transferred in utero because of potential complications. The overall mortalities for each group were 14%, 38%, and 18% respectively. These differences were significant, but when they were corrected for gestation, birth weight, and mode of delivery there was no difference in either the mortality or the incidence of intraventricular haemorrhage in the three study populations. Although there seem to be no distinct advantages of in utero transfer in terms of mortality and morbidity, there are other psychological and emotional advantages.     

Subcapsular hematoma of the liver in infants of very low birth weight.

Between January 1982 and May 1986 a large subcapsular hemorrhage of the liver (SHL) was diagnosed in six infants who weighed 1000 g or less at birth at Royal Alexandria Hospitals, Edmonton. The diagnosis of a ruptured SHL was made between 4 and 18 days of life by means of clinical and sonographic findings in four of the infants; an intact SHL was diagnosed at autopsy in the other two. None of the cases was associated with parenchymal rupture of the liver. Thrombocytopenia was present in five of the six infants and in all four infants with hemoperitoneum. Other possibly relevant antecedent events included mechanical ventilation (in all six), administration of indomethacin (in all six), hypoxia (in five), bilateral pneumothorax necessitating repeated pleural drainage (in three), external cardiac massage (in three) and septicemia (in two). Two of the three infants who underwent surgery survived the operation but later died of unrelated events. One infant who was managed conservatively also survived. A large SHL should be considered in all infants of very low birth weight with unexplained hypovolemia or anemia.     

低出生体重儿肠道微生态研究与展望

低出生体重儿是新生儿中的特殊群体,由于各器官等方面发育相对不成熟,胎龄小,体重轻,患病机率大,早期死亡率高,需要临床更多的干预,这些干预易影响到肠道菌群的正常构建及平衡、影响疾病的治疗及患儿的正常发育,因此探索低出生体重儿肠道微生态的构建规律及影响因素,对指导临床合理喂养及规范治疗具有十分重要的意义。     

低出生体重儿肠道微生态构建影响因素的动态监测

目的 动态监测低出生体重儿肠道菌群,分析不同体重、不同喂养方式及疾病状态等因素对患儿肠道微生态的影响,为规范临床低出生体重儿宫外营养支持措施及治疗手段提供依据。方法 应用16S rRNA荧光定量PCR技术检测正常新生儿和低出生体重儿生后第1、3、7天粪便中大肠埃希菌、肠球菌、乳杆菌及双歧杆菌的含量。结果 （1）在生后7 d内,无论正常新生儿还是低出生体重儿,其粪便中大肠埃希菌、肠球菌、乳杆菌和双歧杆菌的含量均随日龄的增加而增加,且生后7 d内正常新生儿的粪便中大肠埃希菌、肠球菌、乳杆菌和双歧杆菌的含量均显著高于低出生体重儿（P<0.05）,正常新生儿生后7 d内粪便中各细菌的增长率均高于低出生体重儿。（2）体重2 000~2 500 g的低出生体重儿粪便中大肠埃希菌和肠球菌在各日龄中的含量明显高于体重<2 000 g的新生儿（P<0.05）;同时其粪便中双歧杆菌和乳杆菌含量在3日龄和7日龄阶段明显高于体重<2 000 g的新生儿（P<0.05）。（3）3日龄和7日龄母乳喂养组的低出生体重儿粪便中双歧杆菌和乳杆菌含量明显高于乳制品喂养组（P<0.05）;且母乳喂养组新生儿生后7日内粪便中大肠埃希菌、乳杆菌和双歧杆菌含量的增长率均高于乳制品喂养组,尤其是双歧杆菌的增长率（126.49% vs 54.81%）。（4）合并并发症的3日龄和7日龄的低出生体重儿,粪便中乳杆菌和双歧杆菌含量均明显低于无合并症的低出生体重儿（P<0.05）;且无并发症组的低出生体重儿其粪便中肠球菌、乳杆菌和双歧杆菌的增长率均高于有并发症组的低出生体重儿,大肠埃希菌增长率则低于有并发症组。结论 低出生体重儿肠道菌群的定植时间晚且数量少,体重、喂养方式及有无并发症是影响新生儿肠道菌群丰度的重要因素。母乳喂养可促进低出生体重儿肠道中益生菌的定植。疾病因素会导致肠道菌群丰度的降低,使肠道菌群紊乱,其程度可能与病情的严重程度相关。     

Correlation of PP and PR intervals in premature low birth weight infants.

We examined the developmental change by which autonomic neural activity associated respiration modulates spontaneous firing rate of sinus (SA) node and atrioventricular (AV) conduction in premature infants born with low birth weight (LBWI). The purpose of this study was to clarify whether variation of PR is correlated with that of PP or those are independent in LBWI with immature autonomic nervous system. We investigated, therefore, whether there are spontaneous functional differences in the innervation of SA and AV nodes. Further, we evaluated the maturation of autonomic nervous system progressing in the period, on the day of birth (Day 0) to approximately one month after the birth (Month 1). This study was performed in thirteen LBWI during deep sleep. EEG, EOG, ECG, respiratory waves were digitized on line, spontaneous firing cycle of SA node (PP), and AV nodal conduction time (PR) that were recorded on Day 0 and Month 1. Then, the data were analyzed as follows: 1) correlations among the means and standard deviations (SD) of PP, PR and RR, 2) variance evaluation of PP and PR intervals by Lorenz plot analysis method, 3) correlation analysis among PP, PR and RR intervals by linear regression method and 4) frequency analysis for PP and PR intervals by high-speed Fourier transform method (FFT) and determination of frequency density. The PP interval decreased as growing in the period. Contrary PR interval increased. In LBWI, the automatic nervous activities including parasympathetic nerve activity for spontaneous firing cycle of SA node and ventricular excitation cycle on Month 1 were higher than Day 0. It was assumed that the vagal nerve activity for the AV conduction was enhanced. However, there was no significant change in linear regression slope for the spontaneous firing cycle of SA node and the AV conduction time. Postnatal LF/HF changes for PP and PR obtained by frequency analysis, were opposite. Therefore, it was suggested that the maturity of autonomic nervous system progresses in the period, Day 0 to approximately Month 1, but the variations in PP and PR are independent each other.     

低出生体重儿肠道菌群及肠道屏障功能的研究

目的 研究低出生体重儿的肠道菌群分布情况和肠道屏障功能的变化。方法 以低出生体重儿（1 500 g≤体重＜2 500 g）为研究对象,采用16S rRNA荧光定量PCR技术和JY-DLT肠道屏障功能分析系统检测低出生体重儿出生后第7天粪便中双歧杆菌、乳杆菌、大肠埃希菌、肠球菌4种细菌的含量以及血清中的二胺氧化酶、D-乳酸和细菌内毒素的浓度,比较正常新生儿与低出生体重儿肠道菌群和肠道屏障功能的差异,分析不同喂养方式、并发症对低出生体重儿肠道菌群及肠道屏障功能的影响。结果 （1）低出生体重儿组粪便中大肠埃希菌、肠球菌、乳杆菌、双歧杆菌含量均明显低于健康新生儿组（P＜0.05）,血清中二胺氧化酶、D-乳酸高于健康新生儿组（P＜0.05）,细菌内毒素水平差异无统计学意义（P＞0.05）。（2）母乳喂养组低出生体重儿粪便中双歧杆菌和乳杆菌含量明显高于乳制品喂养组（P<0.05）,且血清中二胺氧化酶和和D-乳酸含量低于乳制品喂养组（P<0.05）,细菌内毒素水平差异无统计学意义（P＞0.05）。（3）无并发症组低出生体重儿粪便中乳杆菌和双歧杆菌含量明显高于有并发症组（P＜0.05）,其血清中二胺氧化酶、D-乳酸和细菌内毒素水平均低于有并发症的低出生体重儿（P＜0.05）。结论 低出生体重儿的肠道菌群和肠道屏障功能都与正常新生儿存在差异,母乳喂养有助于肠道有益菌的定植和肠道屏障功能的恢复。     

Effects of parenteral lipid infusion on DNA damage in very low birth weight infants

Very low birth weight (VLBW) infants are known to have poorly developed antioxidant system and may be at increased risk for radical damage. Previous studies have reported higher levels of lipid peroxide products in lipid emulsion used for parenteral nutrition. To examine the direct effects of parenteral lipid infusion on DNA damage in VLBW infants, we measured urinary 8-hydroxydeoxyguanosine (8-OHdG) levels in VLBW infants before, during, and after the parenteral lipid infusion. In both the lipid-infused and lipid-free groups, urinary 8-OHdG excretion levels at 14 days old were significantly (p < 0.01) lower than those at 2 and 7 days old. However, there were no significant differences in urinary 8-OHdG excretion levels between the lipid-infused and lipid-free groups at 2, 7, and 14 days old. Our results suggest that parenteral lipid infusion does not cause oxidative DNA damage, but irrespective of the infusion DNA damage during the first week of life is enhanced when compared with 14 days after birth in VLBW infants.     

Incidence of low birth weight infants born to mothers with multiple risk factors

Low birth weight (LBW) is associated with a large number and variety of risk conditions during pregnancy. The number and types of risk conditions per pregnancy were determined in 1,864 white and 872 black mothers delivered at the University of Kansas Medical Center between 1975 and 1978. The incidence of LBW infants increased steadily among white and black mothers as the number of risk factors increased from none to three or four per pregnancy. Among pregnancies without spontaneous premature rupture of membranes (PROM), 51 percent of the LBW infants were born to mothers who had multiple risk factors associated with their pregnancies, even though only 18 percent of these pregnancies were associated with multiple risk factors. Among pregnancies with PROM, 72 percent were associated with multiple risk conditions, and 31 percent resulted in LBW infants. About 90 percent of LBW infants from PROM pregnancies had mothers with multiple risk factors. For all numbers of risk conditions, black mothers had a higher incidence of LBW infants than white mothers. Among black mothers without spontaneous premature rupture of membranes (PROM), the incidence of LBW infants increased from 3.2 percent (10/308) in low (zero)-risk condition pregnancies to 33 percent (16/49) among mothers with three or four risk conditions during the pregnancy. Among white mothers without PROM, the incidence of LBW infants increased from 1.7 percent (12/708) in low (zero)-risk condition pregnancies to 30 percent (19/64) in pregnancies with three or four risk conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early discharge of infants of low birth weight: a prospective study.

A total of 495 African infants of low birth weight were discharged from Harari Maternity Hospital, Salisbury, between October 1972 and September 1973. Criteria used for discharge were (a) no clinical evidence of disease, (b) satisfactory feeding by mouth (breast or bottle or both), and (c) stable temperature control under normal room conditions. Of the 495 babies 264 fulfilled these criteria when they weighed 1801-1900 g (group 1), 99 when they weighed 1901-2000 g (group 2), and 132 (group 3) when they weighed 2001-2500 g. The overall follow-up rate of those infants living in greater Salisbury was 85-5%, the health visitor playing an important contributory role in their progress, especially those in group 1. More than two clinic visits in the first four to five weeks after discharge were essential for continuing weight gain in groups 1 and 2 but not in group 3. The mean daily weight gain for all babies at the end of four to five weeks was 26 g. Readmission rates for babies in groups 1,2, and 3 were 9-5%, 1%, and 0-8%, respectively, the largest single cause for readmission being bronchopneumonia associated with hypothermia. Altogether 60% of the readmissions occurred during the two winter months (June and July). Hypothermia, associated with low environmental temperatures played a significant part in morbidity and mortality, and twins, particularly in group 1, had a mortality rate three times greater than singletons in the same group. In general, even in underdeveloped communities singleton babies born outside the winter months with reasonable clinic or home visiting facilities can be discharged at a weight of 1800 g or more.     

T cell cytokines and the risk of blood stream infection in extremely low birth weight infants

Cytokines mediate the host immune response to infectious micro-organisms. The objective of this study was to determine whether immune regulatory interleukins (IL-4, IL-5, IL-6, and IL-10) and inflammatory cytokines (Interferon-γ [INF-γ], tumor necrosis factor-β [TNF-β], IL-2, and IL-17) are associated with an increased risk of developing blood stream bacterial/fungal infection (BSI) in extremely low birth weight (ELBW) infants. ELBW infants from 17 NICHD Neonatal Research Network centers without early onset sepsis were studied. Cytokines were measured from blood on days 1, 3, 7, 14, and 21 after birth. 996 ELBW infants contributed a minimum of 4080 unique measurements for each cytokine during the five sampling periods. Infants with BSI had lower levels of the inflammatory cytokines IL-17 (p=0.01), and higher levels of the regulatory cytokines, IL-6 (p=0.01) and IL-10 (p<0.001). Higher levels of regulatory cytokines relative to pro-inflammatory cytokines were associated with increased risk of BSI even after adjusting for confounding variables. In ELBW infants, the ratio of immune regulatory cytokines to inflammatory cytokines was associated with development of BSI. Altered maturation of regulatory and inflammatory cytokines may increase the risk of serious infection in this population.     

Beyond bacteria: a study of the enteric microbial consortium in extremely low birth weight infants

Extremely low birth weight (ELBW) infants have high morbidity and mortality, frequently due to invasive infections from bacteria, fungi, and viruses. The microbial communities present in the gastrointestinal tracts of preterm infants may serve as a reservoir for invasive organisms and remain poorly characterized. We used deep pyrosequencing to examine the gut-associated microbiome of 11 ELBW infants in the first postnatal month, with a first time determination of the eukaryote microbiota such as fungi and nematodes, including bacteria and viruses that have not been previously described. Among the fungi observed, Candida sp. and Clavispora sp. dominated the sequences, but a range of environmental molds were also observed. Surprisingly, seventy-one percent of the infant fecal samples tested contained ribosomal sequences corresponding to the parasitic organism Trichinella. Ribosomal DNA sequences for the roundworm symbiont Xenorhabdus accompanied these sequences in the infant with the greatest proportion of Trichinella sequences. When examining ribosomal DNA sequences in aggregate, Enterobacteriales, Pseudomonas, Staphylococcus, and Enterococcus were the most abundant bacterial taxa in a low diversity bacterial community (mean Shannon-Weaver Index of 1.02 ± 0.69), with relatively little change within individual infants through time. To supplement the ribosomal sequence data, shotgun sequencing was performed on DNA from multiple displacement amplification (MDA) of total fecal genomic DNA from two infants. In addition to the organisms mentioned previously, the metagenome also revealed sequences for gram positive and gram negative bacteriophages, as well as human adenovirus C. Together, these data reveal surprising eukaryotic and viral microbial diversity in ELBW enteric microbiota dominated bytypes of bacteria known to cause invasive disease in these infants.