Decreased antihaemophilic globulin and leucocyte response to epinephrine in preterm infants

Twenty-one preterm and 23 term neonates, 13 splenectomized children and one with congenital asplenia, and 20 normal children were examined for plasma antihaemophilic activity and for blood leucocyte levels before and 30 minutes after a subcutaneous injection of epinephrine 0-01 mg/kg. The basal values for antihaemophilic activity were similar for the 4 groups. The response to epinephrine was a trivial rise in antihaemophilic activity in the preterm group, while the rise in the term newborns was comparable to that of the normal children. The asplenic children all showed a trivial rise. The leucocyte response was also negligible in both the preterm neonates and asplenic groups, while in the term infants it was comparable to that seen in the normal children. These results may indicate an incapacity of the preterm newborn infant's reticuloendothelial system and spleen to react to other challenges, such as bacterial infection.     

Wheezing in infants: the response to epinephrine

There is significant controversy about the role of bronchodilator therapy for wheezing in infants. A double-blind, randomized trial of subcutaneous epinephrine upsilon normal saline was conducted in children less than 24 months of age evaluated at Yale-New Haven Hospital. Respiratory assessments using a newly developed Respiratory Distress Assessment Instrument were made at baseline and 15 minutes after each of two injections. Relief of respiratory distress was assessed using strict a priori criteria based on changes in respiratory rate, wheezing, and retractions as scored in the Respiratory Distress Assessment Instrument. Significantly more children improved their respiratory status with epinephrine (nine of 16) than placebo (one of 14) (Fisher exact test, P = .0067). Paired data in individuals receiving placebo and then epinephrine confirmed this (Wilcoxon signed ranks test, P less than .01). Sixty-three percent of patients less than 12 months and 92% of those 12 to 24 months improved with epinephrine, as did seven of ten children with respiratory syncytial virus bronchiolitis. In many children, response to the initial epinephrine injection was not indicative of final response. Results of this study demonstrate the effectiveness of epinephrine in the treatment of acute wheezing in children less than 24 months of age.     

Decreased ventilation in preterm infants during oral feeding

As respiratory difficulty may accompany nipple feeding in preterm neonates, we studied the effect of oral feeding on ventilation in 23 preterm infants. The infants composed two groups based on their postconceptional age at the time of study: Group A comprised 12 infants 34 to 35.9 weeks of age, and group B, 11 infants 36 to 38 weeks. Ventilation was measured via a nasal mask pneumotachometer, and sucking pressure via a nipple that also permitted milk delivery; transcutaneous PO2 and PCO2 were continuously monitored. The feeding pattern comprised an initial period of continuous sucking of at least 30 seconds, followed by intermittent sucking bursts for the remainder of the feed. When compared with an initial semi-upright control period, minute ventilation (V1) during continuous sucking fell by 52 +/- 6% (P less than 0.001) and 40 +/- 2% (P less than 0.001) in groups A and B, respectively. This was the result of a decrease in respiratory frequency and tidal volume and was associated with a fall in TcPO2 of 13 +/- 4 mm Hg (P less than 0.01) in group A and 10 +/- 2 mm Hg (P less than 0.01) in group B. During intermittent sucking, V1 and TcPO2 recovered partially only in the more mature infants (group B). At the end of the feed, TcPCO2 have risen by 3 +/- 1 mm Hg (P less than 0.001) in group A and by 2 +/- 2 mm Hg (P less than 0.05) in group B. Thus oral feeding results in an impairment of ventilation during continuous sucking and the subsequent recovery during intermittent sucking is dependent on postconceptional age.     

早产儿中性粒细胞活性氧代谢的研究

目的：该研究通过对于不同胎龄新生儿中性粒细胞活性氧代谢水平的检测研究,以了解新生儿中性粒细胞功能发育成熟的过程,并探讨早产儿对于细菌高易感性的部分原因。方法：选择早产儿35例,分为胎龄32周以下和33～36周两组,并选择足月新生儿23例作为对照组。在新生儿出生后取脐静脉血进行体外实验,分别以金黄色葡萄球菌和大肠杆菌刺激诱导呼吸爆发后用超氧阴离子特异性探针氢化溴乙非锭进行细胞内染色,通过流式细胞仪检测中性粒细胞超氧阴离子阳性细胞比率和产生水平;同时对两组不同胎龄早产儿细菌感染实际发生情况进行比较。结果：胎龄32周以下早产儿超氧阴离子阳性中性粒细胞比率与胎龄32周以上早产儿和足月新生儿相比差异有显著性,呈明显低下状态［金黄色葡萄球菌:（79.4±8.6）% vs （89±6.1）% vs （91.3±3.8）%,F＝18.05,P＜0.01;大肠杆菌: （78.2±7.8）% vs （89.3±5.3）% vs （92±4.1）%,F＝28.3, P＜0.01)］;而且阳性率和早产儿胎龄大小密切相关(y＝2.66 x ,P＜0.01);但3组不同胎龄的新生儿活性氧代谢阳性细胞超氧阴离子产生水平之间的差异无显著性。临床观察发现小胎龄早产儿组全身性细菌感染实际发生率高于大胎龄组早产儿。结论：新生儿中性粒细胞细菌诱导活性氧代谢的总体能力直接和新生儿成熟度相关,在胎龄小于32周早产儿中处于明显低下状态,并随着胎龄的增加逐渐成熟。早产儿中性粒细胞活性氧代谢水平的总体低下是导致早产儿细菌感染高易感性的重要原因之一。［中国当代儿科杂志,2007,9（4）：355-357］     

Catecholamine response to chest physiotherapy and endotracheal suctioning in preterm infants

Adrenaline and noradrenaline was measured just before and just after chest physiotherapy and endotracheal suctioning in 13 preterm, ventilated, newborn infants. Mean aortic blood pressure was also recorded. Eight of the infants received phenobarbitone. Catecholamine levels were five-fold higher in the 5 infants with blood pH less than 7.30 compared to the other 8 infants. After the procedure, both adrenaline and noradrenaline were significantly higher than baseline levels. The adrenaline response to the procedure was a two-fold increase and significantly greater than the noradrenaline response. Analysis of the effects of phenobarbitone treatment and acidosis on catecholamine responses by multiple linear regression demonstrated that the adrenaline response was reduced by phenobarbitone while the noradrenaline response was unaffected. There were no associations of blood pressure, responses with catecholamine responses, with acidosis or with phenobarbitone treatment.     

Detectability of auditory evoked response components in preterm infants.

In determining the detectability of brainstem, middle latency and cortical auditory evoked responses in preterm newborns, one has to deal with the ongoing maturation of the auditory system. In the preterm period the detectability of evoked responses is closely related to the appearance of the individual evoked response components. The detectability of the individual evoked response components in preterm infants is important, because low detectability rates make the absence of a particular evoked response component irrelevant with respect to the clinical-neurophysiological correlation. In a longitudinal study we determined the detectability and cumulative detectability, i.e. the presence of individual evoked response components in one or more recordings of evoked response components in 37 low risk preterm infants between 30 and 41 weeks conceptional age (CA). On the basis of their detectability it is concluded that evoked response components, determined between 30 and 34 weeks CA, are generally of limited use for clinical application, except for auditory brainstem response (ABR) components I, IIn, V and Vc and middle latency response (MLR) component Na. Our study made clear that improvement can be achieved by performing more than one examination within a period of approximately 4 weeks between the recording sessions. The cumulative detectability rates after two recordings showed improvement for all components involved in this study. The cumulative detectability rates of ABR components I, II, IIN, III, V, IIc, IIINc, Vc, MLR components Na and P0, and auditory cortical response (ACR) components PbP1 and N2p are sufficient to use as measures in the neurophysiological judgement of functional integrity of the central auditory pathway in preterm infants.     

Biphasic response of respiratory frequency to hypercapnea in preterm infants

The time course of the transient ventilatory response to a sudden change in inspired gas from room air to 4% CO2 in air was examined in 11 healthy preterm neonates. Changes in minute ventilation (VI), tidal volume (VT), and respiratory frequency (f) were determined over 4 to 5 min of CO2 inhalation during both quiet (QS) and active sleep (AS) in each infant. In both states there was a brisk increase of mean VI in response to 4% CO2, while mean VT increased more slowly and mean f only increased transiently at 1 to 2 min. Exponential curve fitting to the change in VI and VT for each infant accounted for 64 +/- 20% of the variance in VI during QS as compared to 30 +/- 18% during AS (p less than 0.003). In only six infants did exponential curves fitted to the changes in VI and VT during QS reach 90% of their steady state values within 4 to 5 min of CO2 exposure. Their time to reach 90% of steady state was always shorter for VI than VT (p less than 0.01). Frequency showed a biphasic response with a transient rise at 1 to 2 min (p less than 0.05) and return to control levels at steady state. These data indicate that not all preterm infants reach a new level of steady state ventilation within 4 to 5 min of 4% CO2 inhalation. Furthermore, many infants exhibit a biphasic response of f over time which causes VI to reach steady state prior to VT.     

Studies in renal response to various protein intakes in preterm infants

The renal effects of two diets--breast-milk and breast-milk with extra human protein (7 g/l breast-milk)--were compared in very low birth weight infants with a gestational age of 26 to 30 weeks. When the infants were given the high protein diet for one week the glomerular filtration rate (GFR) increased significantly more than when breast-milk alone was given. Sodium clearance showed a similar increase in proportion to the GFR during the two diets. The high protein diet raised the urine osmolality moderately in all individuals, while the diuresis remained unchanged. The data in the present study indicate that the function of the immature kidney is influenced by the amount of protein in the diet. However, the long-term renal effects in preterm infants maintained on a high protein intake remain unknown.     

Early pituitary-adrenal response and respiratory outcomes in preterm infants

OBJECTIVE: To assess the influence of circulating (basal) and stimulated plasma adrenocorticotrophin (ACTH) and serum cortisol on the duration of oxygen supplementation and development of chronic lung disease (CLD) in preterm, very low birthweight infants. METHODS: A total of 226 human corticotrophin releasing hormone stimulation tests were performed on 137 very low birthweight infants on days 7 and 14 in a tertiary neonatal centre. RESULTS: Multivariate regression analysis showed that the duration of oxygen supplementation was negatively associated with birth weight, but positively associated with alveolar-arterial oxygen gradient (A-aDO(2)) on the first day and with basal serum cortisol on day 14. In addition, the multivariate classification and regression trees model indicated that the two most useful indices for predicting CLD were clinical risk index for babies (CRIB) score (> 9) and peak serum cortisol (> 740 nmol/l) on day 14. The sensitivity, specificity, positive and negative predictive values of these factors for predicting CLD were 53%, 80%, 81%, and 70% respectively. CONCLUSIONS: The findings suggest that birth weight, severity of initial respiratory failure as reflected by the A-aDO(2) gradient, and continuing "stress" with persistent increase in serum cortisol on day 14 are significant risk factors associated with the duration of oxygen supplementation, whereas early pituitary-adrenal response (basal and peak plasma ACTH and serum cortisol on day 7) is not an independent risk factor. Although CRIB score in combination with peak serum cortisol on day 14 are useful predictors of CLD, the need to use a stimulation test and the relatively late timing of the forecast render these indices unattractive for routine clinical use.     

Stress response and mode of ventilation in preterm infants

AIM—To assess the change in stress response in preterm babies changed from patient triggered ventilation (PTV) to conventional mandatory ventilation (CMV) and vice versa; to determine outcome in relation to stress hormone concentrations.METHODS—A randomised controlled study was conducted in two district general hospital neonatal intensive care units. Thirty babies, treated initially with CMV, were randomly assigned to remain on CMV or to change to PTV. A second group of 29 babies, treated initially with PTV, were randomly assigned to remain on PTV or to change to CMV. The babies were less than 32 weeks of gestation, ventilated within 72 hours of birth, with clinical and radiological features compatible with respiratory distress syndrome (RDS). Stress hormone concentrations and clinical distress score were measured before and 20 minutes after allocation of mode of ventilation. RESULTS—Babies changed from CMV to PTV had significantly reduced adrenaline concentrations (median change ?0.4 nmol/l) compared with those who remained on CMV. There was no increase in adrenaline in babies changed from PTV to CMV. There were no significant changes in noradrenaline concentrations or clinical distress score. Babies who died had significantly higher adrenaline and noradrenaline concentrations than those who survived.CONCLUSION—A change in mode of ventilation significantly reduces adrenaline concentrations. Raised catecholamine values are associated with a poor outcome.     

Weight gain: a response to transfusion in selected preterm infants

A group of low-birth-weight infants with daily weight gains that were below the expected mean for postnatal age were examined to determine the effects of RBC transfusion on their weight gain. The mean hemoglobin concentration (+/- SD) in 13 infants (birth weight less than 1,500 g) prior to transfusion was 8.5 +/- 1.6 g/dL and 11.4 +/- 2.1 g/dL after transfusion. When a comparison was made between the daily weight gain for the week prior to transfusion with the week following transfusion, the mean daily weight gain (+/- SD) increased from 20.8 +/- 4.6 g to 28.0 +/- 6.3 g. Among the six infants with pretransfusion hemogloblin concentrations of less than 7.5 g/dL, the increase in daily weight gain was greatest (a rise from 22.6 +/- 4.0 g to 34.1 +/- 4.9 g). Improvements in weight gain were associated with a decrease in metabolic rates as determined by declines in oxygen consumption.     

Thrombopoietin in preterm infants: gestational age-dependent response

PURPOSE: To investigate the factors affecting thrombopoietin (TPO) levels in preterm infants and to determine if TPO levels differ in infants born to mothers with preeclampsia and those infants with culture-proven sepsis. METHODS: Serial serum samples (N = 95) were obtained from 27 infants less than 33 weeks' gestation. Samples were analyzed for TPO using enzyme-linked immunosorbent assay. All samples had an accompanying complete blood count. Analysis of variance with post hoc analysis by least significant difference test, Mann-Whitney test, or chi2 was used to compare groups, as appropriate. Forward, stepwise linear regression was used to account for potential confounding variables. Data are expressed as mean +/- SD. RESULTS: TPO levels were not significantly correlated with the absolute platelet counts (R = -0.04, P = 0.69). TPO levels were significantly correlated with gestational age (R= 0.50, P < 0.001) when the platelet count was less than 150,000/mm3. TPO levels were significantly elevated in infants with platelets less than 150,000/mm3 born to mothers with preeclampsia compared with infants with sepsis (1184 +/- 98 vs. 579 +/- 363 pg/mL, P < 0.01). After adjusting for confounding variables using multivariate analysis (model: r2 = 0.43, P < 0.01), gestational age (r2 = 0.26) and preeclampsia (r2 = 0.03) remained significantly associated with TPO levels, whereas sepsis did not contribute to the variability of TPO. CONCLUSIONS: TPO response of infants with platelets less than 150,000/mm3 is dependent on gestational age. Infants with thrombocytopenia associated with preeclampsia have increased circulating levels of TPO. Infants with thrombocytopenia secondary to sepsis do not show an increase in TPO, but this appears to be an effect of low gestational age.     

Monocytosis in preterm infants.

In sick preterm neonates receiving intensive care a spectacular rise in monocyte count has frequently been observed in sequential full blood examinations. The etiology of this has not previously been investigated and this study examines clinical factors that may contribute to this finding. Thirty (5.1%) of the 587 neonates who required intensive care during the study period had significant monocytosis (absolute count greater than 1700/mm3). Their mean gestation was 29 weeks (range 26-32 weeks). Monocytic response occurred at an age of 5.5 +/- 3 (mean +/- S.D.) days with 20% occurring at birth, 57% in the first week and 23% in the second week of life and lasted for 19.8 +/- 16 days (mean +/- S.D.). Most reached peak levels within two weeks and these ranged between 2,170 and 7176 per mm3. Analysis of the clinical variables against 37 controls revealed lower mean birth weight and gestational age, and higher incidence of leukocytosis, multiple transfusions, albumin infusions and theophylline therapy in the study group in comparison to the controls (P less than 0.001). No significant difference was found in maternal risk factors (pre-eclampsia, diabetes and amnionitis), birth asphyxia, respiratory disease, parenteral nutrition, proven infection and antibiotic therapy. An unexpected association with maternal steroid therapy was demonstrated. It is speculated that monocytosis represents a physiological though immature response of the marrow of small premature infants to a variety of exogenous stimuli including drugs and foreign protein infusions.     

Immune response to Haemophilus influenzae type b conjugate vaccine in preterm infants

Background: Haemophilus influenzae type b (Hib) vaccine became available for use in Japan in December 2008. The aim of the present study was to evaluate the immunogenicity of Hib vaccine in Japanese preterm infants. Methods: Serum samples were obtained from 54 preterm infants before the first vaccination and 1 month after the third. Anti‐polyribosylribitol phosphate (PRP) antibodies were measured using an enzyme‐linked immunosorbent assay method. Antibody positivity was defined as levels >1 µg/mL. Results: Of the 54 preterm infants, 46 (85.2%) achieved antibody levels >1 µg/mL. This compares with the 92.4% reported in full‐term infants. The antibody seroconversion rate of infants starting vaccination at 2 months of age was close to being significantly lower than when vaccination was started at 3 months of age (P= 0.060). In addition, the percentage of infants achieving a positive response in the group with a history of antenatal steroid exposure was significantly higher than in those not exposed (P= 0.046). Thus, risk factors for lower Hib antibody concentrations after three doses of vaccine were age at first vaccination and lack of use of antenatal steroids. Conclusions: There is a possibility that perinatal factors and the environment unique to preterm infants are related to their lower antibody positivity rates compared to full‐term infants. It may therefore be preferable to modify the proposed immunization schedule.     

Intrauterine growth retardation and brainstem auditory-evoked response in preterm infants

Intrauterine growth retardation is frequently associated with intrauterine undernutrition, and can deleteriously affect brain function. Twenty-eight premature small for gestational age infants were compared with 28 premature appropriate for gestational age infants to determine whether intrauterine growth retardation was associated with abnormalities in the auditory pathway in the early neonatal period. The auditory pathway was studied between 4-18 wk of life by analysis of brainstem auditory-evoked potentials elicited by a 10/s 75 decibel above normal adult hearing level (dB nHL) click stimulus presented at the infants' ears. Peak latencies of components I, III and V, and interpeak latencies I-III, III-V and I-V, yielded no statistically significant differences between groups. The present study indicates that intrauterine growth-retarded premature infants may not have abnormalities of brainstem auditory-evoked response in the early neonatal period.     

Plasma dopamine, norepinephrine, epinephrine and DOPAC levels in preterm infants prior to and immediately after a sleep ventilation hypercarbia test.

The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates (n = 8), and in sick preterm neonates with respiratory disorders (n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3-4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide-21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension (r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p less than 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores.