Effect of blood transfusions on cerebral haemodynamics in preterm infants

Aim: To assess the possible cerebral haemodynamic changes occurring in preterm infants after blood transfusions. Methods: Preterm infants who had undergone blood transfusions were prospectively studied using both near infrared spectroscopy and cerebral Doppler ultrasonography. Results: Fourteen infants (mean gestational age 29.6 wk, SD 2.6; mean birthweight 1430 g, SD 332) were studied at the mean age of 29 (SD 14) d. A significant increase in oxygenated haemoglobin (O 2 Hb), deoxygenated haemoglobin (HHb), mixed cerebral oxygen saturation (SmO 2 ) and change in cerebral blood volume occurred after transfusion. Between ultrasound parameters, we found a decrease in diastolic velocity and an increase in resistance index.

Conclusion: Blood transfusions improve cerebral oxygen supply and induce a decrease in cerebral blood volume, probably due to an increase in cerebral vessel resistance.     

Reducing donor exposure in preterm infants requiring multiple blood transfusions.

Preterm infants frequently require multiple blood transfusions. Traditionally, ''fresh'' (less than seven days old) blood has been used but this often results in transfusions from multiple donors. To reduce donor exposure the policy for top-up transfusions was changed. A unit of blood under five days old with additional satellite packs was ordered for each infant and used up to its expiry date, allowing up to eight transfusions from a single donation to be given. The mean (SD) number of transfusions per infant in 43 infants transfused according to previous policy and in 29 transfused according to the new policy was similar at 5.6 (4.0) and 5.3 (3.1), respectively. However, donor exposure fell following the change in policy from 4.9 (3.5) to only 2.0 (0.9). Only one infant was exposed to more than three donors compared with 24 infants in the control group. Plasma potassium concentrations were not significantly different following transfusion of blood stored for up to 33 days. This simple change in policy has reduced donor exposure in infants requiring multiple top-up transfusions.     

Plasma bilirubin level and oxidative stress in preterm infants

OBJECTIVE: To assess the hypothesis that changes in plasma total bilirubin levels (Btot) can influence the antioxidant system and oxidative stress in preterm infants. METHODS: Twenty two healthy preterm infants who presented with visible non-haemolytic hyperbilirubinaemia were studied at the mean (SD) age of 3.7 (1.5) days. Btot, plasma total hydroperoxide concentration (TH), plasma protein SH group concentration, and total antioxidant capacity of the plasma (TAC) were measured at study entry and after 24 hours. RESULTS: Btot did not correlate with TH, TAC, or protein SH group concentration, but a significant correlation was found between TH and TAC, TH and protein SH groups, and TAC and protein SH groups, both at study entry and after 24 hours. CONCLUSION: The decrease in plasma bilirubin was contemporary with an increase in plasma antioxidant capacity and decrease in oxidative stress in preterm infants. This may be the result of the pro-oxidant effect of haem oxygenase, mediated by iron release, which may outcompete the antioxidant properties of bilirubin.     

Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants.

To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation.     

Role of heme oxygenase and bilirubin in oxidative stress in preterm infants

In a previous study, it was found that the decrease in the total plasma bilirubin level (Btot) in preterm infants was associated with the decrease in oxidative stress. We hypothesized that this occurs as a result of a pro-oxidant effect of heme oxygenase (HO), which outcompetes with the antioxidant properties of bilirubin. In this study we studied 12 preterm infants in whom the plasma levels of Btot, total hydroperoxide (TH), protein SH groups, HO activity, non-transferrin-bound iron (NTBI), and erythrocyte CuZn superoxide dismutase (CuZn SOD) activity were concurrently measured when the Btot was >220 microM and after a Btot drop of >34 microM. The Btot decrease was concurrent with the TH decrease, protein SH groups increase, and the HO and CuZn SOD activity increase and was not associated with an NTBI increase. We concluded that 1) Btot does not exert a meaningful antioxidant effect in vivo; 2) HO does not exert a pro-oxidant effect involving an NTBI increase and that, on the contrary, it could exert an antioxidant effect; and 3) the concurrent HO and CuZn SOD activity increase could indicate a synergic antioxidant effect of the two enzymes.     

氨茶碱对早产儿血糖影响的时相变化

目的：探讨早产儿输注氨茶碱对血糖影响的时相变化。方法：120例早产儿随机分成4组,每组30例,A组使用氨茶碱时输入5%葡萄糖,B组仅输入5%葡萄糖;C组使用氨茶碱时输入10%葡萄糖,D组仅输入10%葡萄糖。分别于用药后15,30 min和1,1.5,2,4,6,12,24 h测定血糖浓度。结果：①A组使用氨茶碱后15 min血糖有上升趋势,30～120 min左右达到高峰并逐渐下降,4h左右降至接近用药前水平,各测定时间点的血糖值与用药前血糖比较差异无显著性。A组用药后与B组各相应的测定时间点的血糖值比较,差异无显著性。②C组使用氨茶碱后15 min血 糖迅速上升,30～120 min左右达到高峰并逐渐下降,但下降较慢,24h后未能降至用药前水平,各测定时间点的血糖值与用药前血糖比较,差异有非常显著性意义(P<0.01)。C组与D组相应时间点血糖值比较,差异有非常显著性意义(P<0.01)。③使用氨茶碱时输入不同浓度的葡萄糖,对血糖影响的程度不一样。输入5%葡萄糖时,血糖虽然升高,但仍在正常范围内,而输入10%葡萄糖时,血糖升高超过正常范围。A组与C组使用氨茶碱后各测定时间点血糖值比较,在4 h内有显著性差异。结论：氨茶碱在早产儿 中使用是安全的,但使用时输糖浓度应控制在5%左右,输入10%葡萄糖时可引起高血糖。使用过程中应注意监测血糖,尤其是2 h内的血糖。     

早产儿血糖对定量脑电图参数的影响

目的 探讨定量脑电图（qEEG）在评价血糖对早产儿脑功能影响中的价值。方法 选取2019年1~12月中南大学湘雅三医院新生儿科收治的早产儿为研究对象。根据血糖水平分为组1（< 4.95 mmol/L）、组2（4.95 mmol/L~）、组3（6.60 mmol/L~）与组4（≥8.55 mmol/L）,比较各组间qEEG参数的变化,并对血糖与qEEG参数进行相关性分析。结果 共纳入早产儿39例,血糖测定采集点84个。与组4相比,其余各组各脑区总功率、额区和枕区各频带绝对功率均显著增高,差异均有统计学意义（P < 0.05）。各脑区总功率、δ/θ、（δ+θ）/（α+β）比值均与血糖呈负相关（P < 0.05）,θ频带相对功率与血糖呈正相关（P < 0.05）。结论 随着血糖的改变,早产儿总功率、各频带功率及频谱组成均发生变化,qEEG可能成为监测早产儿血糖异常对脑功能影响的重要工具。     

Urinary metabolites of oxidative stress and nitric oxide in preterm and term infants

BACKGROUND: Many neonatal diseases have been associated with oxidative stress and altered nitric oxide status. OBJECTIVE: To determine the effects of clinical interventions on the levels of urinary peroxides, a marker of oxidative stress, and urinary nitrate/nitrites, indices of nitric oxide production and metabolism, in the first 72 h of life in premature infants. METHODS: A single, spot urine sample was collected from 82 premature and 20 healthy term infants within the first 72 h of life. The peroxide levels were quantified using a fluorometric method, and nitrate/nitrite levels were quantified by chemiluminescence. RESULTS: Premature infants had a median peroxide level of 10.0 micromol/mmol creatinine (Cr) (interquartile range 4.8-20.0 micromol/mmol Cr). These values were significantly higher than term infants (median 5.0 micromol/mmol Cr, interquartile range 2.7-10.0 micromol/mmol Cr). Urinary nitrate/nitrite levels were not significantly different between preterm (220.5 micromol/mmol Cr, interquartile range 161-287 micromol/mmol Cr) and healthy term infants (244 micromol/mmol Cr, interquartile range 194-316 micromol/mmol Cr). For urinary peroxides, infants on TPN had significantly higher urinary peroxide levels than infants who were not on TPN at the time of urine collection (p = 0.006). Administration of indomethacin was associated with lower levels of urinary nitrate/nitrites (p = 0.0003). Both effects remained significant after controlling for gestational age, degree of respiratory distress and day of urine collection. CONCLUSION: Monitoring the level of both peroxides and nitrate/nitrite may offer added information about the degree of oxidative stress experienced by a newborn but needs to account for clinical and therapeutic interventions.     

Effect of blood transfusion on cardiorespiratory abnormalities in preterm infants.

The effects of red blood cell transfusion on the incidences of apnoea, bradycardia, tachycardia and oxygen desaturation over periods of 72 hours before and after transfusion were assessed in 25 infants with a gestational age of < or = 32 weeks (mean (SEM) 29.2 (0.4) weeks, birthweight 1170 (73) g; postnatal age at transfusion 39 (4) days). During transfusion haemoglobin rose from 78 (2) g/l to 117 (2) g/l. Significant decreases were observed in daily frequencies of apnoeas longer than 15 seconds (median from 2.7 to 0.9 events a day), tachycardias of more than 200 beats per minute (from 34 to 25 events per day), bradycardias below 100 beats per minute (from 65 to 12 events per day) and 80 beats per minute (from 8.4 to 3.3 events per day). Oxygen saturation improved in 20 of the infants. Transfusion improves cardiorespiration in preterm infants for several days.     

Effect of booster blood transfusions on oxygen utilization in infants with bronchopulmonary dysplasia

To assess the impact of booster transfusions on oxygen utilization in infants with bronchopulmonary dysplasia, we noninvasively measured oxygen consumption (VO2) and the variables of systemic oxygen transport (SOT) before and 24 hours after transfusion therapy in 10 oxygen-dependent infants with bronchopulmonary dysplasia. The infants had been born with a mean gestational age of 27.6 weeks and a mean birth weight of 0.88 kg. Study weight averaged 1.24 +/- 0.35 kg, and study age averaged 5.5 +/- 2.4 weeks. Requirements for fractional concentration of inspired oxygen averaged 0.41 +/- 0.15 to maintain an oxygen saturation of 0.93 +/- 0.02. The VO2 was measured by means of a commercially available analyzer through a flow-through circuit and pump connected to a hood or in line with the ventilator. Cardiac output was calculated by means of pulsed Doppler ultrasonography. Oxygen saturation was measured by means of transcutaneous pulse oximetry. The coefficient of oxygen utilization was calculated as VO2/SOT. Transfusion consisted of packed erythrocytes (10 ml/kg). Oxygen utilization fell in all subjects after transfusion (p less than 0.01), but it fell more substantially in subjects with higher coefficients of oxygen utilization (r = -0.80, p less than 0.01), suggesting a physiologic benefit in selected patients, particularly those with higher levels of oxygen utilization. There was also a significant increase in overall systemic oxygen transport (p less than 0.01) and decrease in VO2 (p less than 0.02). Hemoglobin levels alone did not correlate with overall systemic oxygen transport, VO2, or level of oxygen use before transfusion, and thus did not predict which subjects would have a physiologic benefit from transfusion as reflected by falls in oxygen utilization.     

Effect of caffeine on cerebral blood flow velocity in preterm infants

A continuous-wave form Doppler monitor was used to examine the effect of caffeine on cerebral blood flow velocity (CBFV) in 7 clinically stable preterm neonates suffering from apnea. Caffeine, in the form of caffeine citrate, or saline were given intravenously at loading doses of 20 mg/kg. Every subject was his own control. Placebo (saline) was systematically injected prior to caffeine citrate. Simultaneous recording of heart rate, arterial blood pressure, respiratory rate, TcPO2, TcPCO2 were made before, then at the end of the injection, and 30, 60 and 120 min after the end of each administration of either placebo or caffeine. Compared with placebo, caffeine injection was not associated with significant changes in CBFV. An increase was found in both heart-rate and respiratory rate (p less than 0.05). Mean arterial blood pressure, TcPCO2 and TcPO2 did not change significantly. Our data suggest that a caffeine citrate loading dose of 20 mg/kg as currently used at the beginning of treatment of apnea in preterm neonates has no effect on CBFV.     

早产儿血糖对定量脑电图参数的影响

目的 探讨定量脑电图（qEEG）在评价血糖对早产儿脑功能影响中的价值。方法 选取2019年1~12月中南大学湘雅三医院新生儿科收治的早产儿为研究对象。根据血糖水平分为组1（< 4.95 mmol/L）、组2（4.95 mmol/L~）、组3（6.60 mmol/L~）与组4（≥8.55 mmol/L）,比较各组间qEEG参数的变化,并对血糖与qEEG参数进行相关性分析。结果 共纳入早产儿39例,血糖测定采集点84个。与组4相比,其余各组各脑区总功率、额区和枕区各频带绝对功率均显著增高,差异均有统计学意义（P < 0.05）。各脑区总功率、δ/θ、（δ+θ）/（α+β）比值均与血糖呈负相关（P < 0.05）,θ频带相对功率与血糖呈正相关（P < 0.05）。结论 随着血糖的改变,早产儿总功率、各频带功率及频谱组成均发生变化,qEEG可能成为监测早产儿血糖异常对脑功能影响的重要工具。     

Effects of exclusive formula or breast milk feeding on oxidative stress in healthy preterm infants

Background

Compared to formula, breast milk is considered to have superior antioxidant properties and consequently may reduce the occurrence of a number of diseases of prematurity associated with oxidative stress.

Aims

To test whether the antioxidant properties of breast milk in healthy premature infants are different to those of formula milk by comparing vitamin E levels in milk and determining the excretion of malondialdehyde (MDA) in urine.

Methods

Vitamin E was measured in the breast milk of 20 mothers who had given birth prematurely. Urinary MDA was measured in 10 exclusively breast milk fed and 10 exclusively formula fed healthy preterm infants receiving no vitamin supplements. MDA was measured after derivatisation with 2,4‐dinitrophenylhydrazine and consecutive HPLC with UV detection.

Results

Urinary MDA concentrations were consistently very low (0.074±0.033 μM/mM Cr and 0.078±0.026 μM/mM Cr in breast and formula fed infants respectively) and not significantly different between healthy breast milk and formula fed infants. Both breast and formula milk contained satisfactory levels (0.3–3.0 mg/100 ml) of vitamin E.

Conclusion

Antioxidant properties of both breast milk and formulae are sufficient to prevent significant lipid peroxidation in healthy premature infants.     

A pilot randomised controlled trial of peripheral fractional oxygen extraction to guide blood transfusions in preterm infants

BACKGROUND: Peripheral fractional oxygen extraction (FOE) may be a better indicator of the need for transfusion than the haemoglobin concentration (Hb) because it is a measure of the adequacy of oxygen delivery to meet demand. A randomised controlled trial of the use of peripheral FOE to guide the need for blood transfusions in preterm infants was carried out to test this hypothesis. METHOD: Infants less than 1500 g birth weight who were stable and less than 2 weeks old were randomised to receive transfusions guided by either a conventional protocol based on Hb (conventional group) or a protocol based on measurements of peripheral FOE made by near infrared spectroscopy (NIRS group). Measurements of Hb and FOE were made on all infants from randomisation until discharge. The primary outcome measures were number of transfusions received, rate of weight gain, and postmenstrual age at discharge. RESULTS: Thirty seven infants were randomised to each group. Birth weight (median, range) (1200, 1004-1373 v 1136, 1009-1285 g) and Hb (median, range) at randomisation (160, 149-179 v 155, 145-181 g/l) did not differ between the two groups. The total number of transfusions given to the NIRS group was 56 and to the conventional group 84. The median number of transfusions per infant, the median volume of blood transfused to each group, and the total number of donors to which infants were exposed were similar in the two groups. Infants transfused according to the conventional protocol were more likely to be transfused earlier and at a higher Hb than those transfused in the NIRS group. Infants in the conventional group spent a significantly shorter period than those in the NIRS group with Hb < 100 g/l. Of the 56 transfusions given to the NIRS group, 33 (59%) were given because of clinical concerns rather than because of high FOE. There was no difference in the rate of weight gain, rate of linear growth, postmenstrual age at discharge, or the incidence of chronic lung disease or retinopathy of prematurity. CONCLUSIONS: FOE measurements failed to identify many infants felt by clinicians to require blood transfusion. This may have been because clinicians relied on conventional indicators of transfusion that are vague and non-specific, or a peripheral FOE of 0.47 alone may not be a sensitive enough predictor of the need for transfusion. This requires further study.     

Effects of exclusive formula or breast milk feeding on oxidative stress in healthy preterm infants.

BACKGROUND: Compared to formula, breast milk is considered to have superior antioxidant properties and consequently may reduce the occurrence of a number of diseases of prematurity associated with oxidative stress. AIMS: To test whether the antioxidant properties of breast milk in healthy premature infants are different to those of formula milk by comparing vitamin E levels in milk and determining the excretion of malondialdehyde (MDA) in urine. METHODS: Vitamin E was measured in the breast milk of 20 mothers who had given birth prematurely. Urinary MDA was measured in 10 exclusively breast milk fed and 10 exclusively formula fed healthy preterm infants receiving no vitamin supplements. MDA was measured after derivatisation with 2,4-dinitrophenylhydrazine and consecutive HPLC with UV detection. RESULTS: Urinary MDA concentrations were consistently very low (0.074+/-0.033 microM/mM Cr and 0.078+/-0.026 microM/mM Cr in breast and formula fed infants respectively) and not significantly different between healthy breast milk and formula fed infants. Both breast and formula milk contained satisfactory levels (0.3-3.0 mg/100 ml) of vitamin E. CONCLUSION: Antioxidant properties of both breast milk and formulae are sufficient to prevent significant lipid peroxidation in healthy premature infants.     

Effect of morphine and pancuronium on the stress response in ventilated preterm infants

Nintey-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 μg/kg per h but was increased to 100 μg/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 μg/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n=29) showed a significant reduction in noradrenaline levels (median change −2.2 nmols/1 (range −47.2 to +7.2 nmols/1), although seven were withdrawn from this group because of failure to settle. Group P (n=28) and group M + P (n=38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.