Dietary nucleotides and intestinal blood flow velocity in term infants

OBJECTIVES: Two previous studies have shown that the addition of nucleotides to single feedings of formula is associated with increased 90-minute postprandial superior mesenteric artery (SMA) blood flow velocity (BFV). To assess the effect of chronic feeding of nucleotide-supplemented formula, we measured pre- and postprandial SMA BFV in term infants fed formula with or without added nucleotides for 4 weeks. METHODS: At 1 week of age, healthy, term infants were randomized to receive formula with added nucleotides (NT+), or formula without added nucleotides (NT-) from age 1 to 5 weeks. When the infants were 5 weeks of age, SMA BFV was measured by Doppler ultrasound 15 minutes before the assigned feeding (baseline) and 30, 60, and 90 minutes after the start of feeding. A reference group of human milk-fed infants was studied before and after breast feeding. RESULTS: Thirty formula-fed (NT+ = 17; NT- = 13) and 10 human milk-fed infants were studied. Baseline BFV was similar among the three groups. BFV increased in each group from baseline to 30 minutes after initiation of feeding and progressively declined from 30 to 90 minutes in infants fed NT- formula or human milk. In infants fed NT+ formula, BFV decreased between 30 and 60 minutes. However, from 60 to 90 minutes, velocity was unchanged or increased. At 90 minutes, mean and peak systolic velocities were significantly greater in the NT+ group than the NT- group (P < 0.001). CONCLUSIONS: These data agree with those of previous studies showing increased 90-minute postprandial SMA BFV after a feeding with nucleotide-supplemented formula. The clinical significance of these findings is unknown.     

Short-term effects of blood transfusion on blood volume and resting peripheral blood flow in preterm infants

The effects of blood transfusion on cardiac output and blood pressure are variable, but resting peripheral blood flow (RPBF) may be a sensitive indicator of changes in blood volume. The purpose of this investigation was to study the effects of red cell transfusion on blood volume (Evans blue), blood pressure, RPBF in the leg (strain-gauge plethysmography) and blood viscosity (cone-plate viscometer) in preterm infants during the first week after birth. Fourteen infants with mean ± SD birth weight of 1658 ± 429 g, gestational age 33 ± 3 weeks and postnatal age 64 ± 40 h received 18 ±4 ml/kg of packed red cells (red cells 11±2 ml/kg, plasma 7± 1 ml/kg) because their hematocrit was less than 0.45 l/l. Mean blood volume before transfusion was 88±15 ml/kg. The increase in blood volume (9 ±4 ml/kg) measured 4 to 6 h after transfusion was smaller than the transfused volume (18 ± 4 ml/kg), due to a shift of plasma to the extravascular space. The plasma shift increased with increasing pretransfusion blood volume ( r = 0.70; p = 0.007). Red cell transfusion caused an increase in RPBF by 25% ( p <0.01), whereas systolic blood pressure (BP) increased by only 12%. Peripheral resistance (R = BP/RPBF) decreased by 9% (p<0.01). Blood viscosity (±) increased by 21'% ( p <0.001) and vascular hindrance (R/±) decreased by 24% ( p < 0.001), indicating vasodilatation of limb arteries. The increase in RPBF and the decrease in hindrance were particularly pronounced in infants with high pretransfusion blood volume. We conclude that the increase in blood volume after transfusion is not proportional to the transfused volume and that RPBF increases more than systolic blood pressure with increasing blood volume. The increase in RPBF can be explained by vasodilatation of limb arteries and by increased blood pressure.     

The influence of dietary nucleotides on erythrocyte membrane fatty acids and plasma lipids in preterm infants

Objective : The objective of this study was to evaluate whether a regular formula for premature infants supplemented with nucleotides has any influence on plasma lipids and erythrocyte membrane fatty acids. Methods : Preterm infants fed either human milk supplemented with human milk protein (HM, n = 14), nucleotide-supplemented preterm formula (NF, n = 13), or a regular preterm formula (F, n = 13) were included in the study. The NF was supplemented with 18.2 mg cytidine monophosphate/1 (CMP), 7.0 mg uridine monophosphate/1 (UMP), 6.4mg adenosine monophosphate/1 (AMP), 3.0mg inosine monophosphate/1 (IMP) and 3.0 mg guanosine monophosphate/1 (GMP). Results : There were significantly higher concentrations of triglycerides (TG) in infants fed NF compared to those fed F (191.42 ± 79.58 vs 108.21 ± 43.73, p < 0.001, mean ± SD lipid concentrations, mg/100ml plasma). Infants fed F had significantly lower concentrations of total cholesterol (94.34 ± 11.71 vs 115.69 ± 39.29, p < 0.01) and TG in plasma (108.21 ± 43.73 vs 172.27 ± 68.19, p < 0.001, mean ± SD lipid concentrations, mg/100ml plasma) when compared to HM-fed infants. There were no significant differences in any of the erythrocyte membrane fatty acids and total long-chain polyunsaturated fatty acids (LC-PUFA) between NF and F during the study period (6 weeks). Furthermore, total LC-PUFA and docosahexaenoic acid (DHA) concentrations in red blood cell were not significantly different when infants fed NF were compared to those fed HM. In contrast, however, infants fed F had significantly lower concentrations of total n-3 LC-PUFA ( p < 0.01) and DHA ( p < 0.01) than those found in HM-fed infants. Conclusions : These results do not suggest an effect of nucleotides on the red blood cell LC-PUFA profile in preterm infants. However, the nucleotides may increase the concentrations of triglycerides in plasma.     

The effect of phototherapy on cerebral blood flow velocity in preterm infants

Cerebral blood flow velocity was studied with two-dimensional/pulsed Doppler ultrasound before, during and after discontinuation of phototherapy in 22 preterm infants (gestational age ≤32 weeks), who were treated for a minimum of 12h with blue-light phototherapy for non-haemolytic hyperbilirubinaemia. Before the cerebral blood flow velocity measurements, patency of the ductus arteriosus was diagnosed by Doppler echocardiography. All infants had normal brain ultrasound scans. Mean cerebral blood flow velocity increased significantly after initiation of phototherapy in all infants. Only in “healthy” (non-ventilated) infants did cerebral blood flow velocity return to pre-phototherapy values (baseline) after discontinuation of phototherapy, whereas in “unhealthy” (ventilated) infants cerebral blood flow velocity did not return to baseline. In 10 infants the ductus arteriosus reopened during phototherapy. In those infants, mean cerebral blood flow velocity returned to pre-phototherapy values after 2h of phototherapy prior to its discontinuation.     

Cerebral blood flow velocity regulation in preterm infants

Cerebrovascular autoregulation is the mechanism by which changes in cerebral blood flow are prevented during fluctuations in mean arterial blood pressure. Doppler ultrasound measurement of cerebral blood flow velocity provides a reliable indirect technique to estimate cerebral blood flow. In 48 stable preterm infants less than or equal to 32 weeks gestation, we studied the mean flow velocity in the pericallosal artery at 12, or at 12 and 72 h of age with two-dimensional/pulsed Doppler ultrasound and correlated the mean flow velocity with the simultaneously obtained mean arterial blood pressure values. Mean flow velocity was stable at a mean arterial blood pressure ranging from 31 to 40 mm Hg, but changed proportionally with mean arterial blood pressure values outside this narrow range. Multiple regression analysis showed that mean flow velocity was primarily determined by mean arterial blood pressure. These data suggest that in preterm infants regulation of cerebral blood flow velocity occurs only over a narrow range of mean arterial blood pressure values.     

The influence of blood transfusion on brain blood flow autoregulation among stable preterm infants

Prior to and 24 h following blood transfusion serial determinations of both cerebral artery flow velocity waveforms and mean arterial blood pressure have been used to reconstruct the autoregulatory curve and its upper blood pressure limit among five stable preterm infants. Prior to transfusion the autoregulatory range of cerebral blood flow (CBF) was narrow due to a relatively low-set upper blood pressure limit. At 24 h after transfusion each individual has been re-examined. Following correction of anemia both a significant reduction of CBF velocities as well as a concomitant rise of the Pulsatility Index (PI) occurred over the entire range of blood pressures indicating a reduction of CBF after transfusion. In addition a right-sided shift of the upper limit towards higher mean blood pressures occurred after transfusion and resulted in an extension of the autoregulatory plateau of CBF. These favourable effects of blood transfusion ameliorating autoregulation of brain blood flow particularly at higher blood pressures might well bear important therapeutic perspectives in our effort to prevent intracranial haemorrhage among sick preterm infants.     

The effects of two extremes of dietary intake on protein accretion in preterm infants

A comparison has been made of protein accretion and growth in premature infants fed banked drip breast milk (BBM) or a preterm formula (PF). Protein accretion was calculated from the difference between dietary nitrogen intake and output in urine and stools, measured in a nutrient balance study. As expected, only the infants fed PF achieved the intrauterine growth rate. However, whilst weight gain in infants fed BBM was 71% of that in the group fed PF, the rate of protein deposition was less than 50%. As a result, the protein concentration in new tissue of infants fed BBM averaged 32% less than in those fed PF and 21% less than the lower end of the range reported to occur in utero. We speculate that infants fed BBM have an abnormally low protein concentration in their lean body mass.     

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.     

Low systemic blood flow and hyperkalemia in preterm infants

OBJECTIVE: Early low systemic blood flow is common in preterm infants. This study examines the relationship among low flow, renal function, and early changes in blood potassium (K(+)). METHODS: Preterm infants (n = 119) born before 30 weeks' gestational age underwent serial Doppler echocardiographic studies. Superior vena cava flow (SVC flow) was assessed as a measure of upper body systemic blood flow uncorrupted by systemic to pulmonary shunts. Serial whole blood K(+) concentrations on each arterial blood gas sample and urinary output in the first 48 hours were recorded. RESULTS: Most infants had a variable degree of rise in K(+) during the first 24 hours of life. The mean rate of rise was 0.17 mmol/L/h, the mean peak K(+) was 5.54 mmol/L, and the mean time of peak K(+) was 20 hours. The peak K(+) occurred after the lowest measured SVC flow in 84% of infants. A significant positive relationship was found between the lowest measured SVC flow and the mean (r = 0.31, P =.001) and peak (r = 0.31, P =.001) K(+) in the first 24 hours. Low SVC flow at 5 hours best predicted the rate of K(+) rise (r = 0.28, P =.002) and at 12 hours best predicted the peak K(+) concentration (r = 0.47, P <.001). The mean minimum SVC flow in the 17 babies who became hyperkalemic was 29.5 mL/kg/min versus 46.2 mL/kg/min in the 102 infants with normokalemia. Urine output in the first 24 hours was significantly lower in the hyperkalemic infants. A K(+) rate rise exceeding 0.12 mmol/L/h in the first 12 hours predicted low SVC flow with 93% accuracy. CONCLUSIONS: The data are consistent with a role for low systemic blood flow leading to reduced urinary output and subsequent hyperkalemia in preterm infants.     

Sex-specific differences in peripheral microvascular blood flow in preterm infants

Microvascular blood flow is related to physiologic instability in newborn preterm infants. We investigated sex-specific differences in basal microvascular blood flow and the ability of the microvasculature to respond to vasoactive stimuli following preterm birth. Ninety-six infants in two gestational age groups (24-28 and 29-36 wk) were studied on days 1-5 of life. Laser Doppler flowmetry was used to measure baseline microvascular blood flow and vasodilatation in response to acetylcholine and local warming. A significant interaction of gestational age and sex was observed for baseline flow at 24 h of age. In the 24-28 wk group, male infants had higher baseline flow than females. Male, but not female, infants born at 24-28 wk exhibited a significant relationship between baseline flow and vasodilatory response to acetylcholine at 24 h of age. By 120 h of age, both sexes exhibited similar responses. Infants born at 24-28 wk exhibited greater vasodilatation in response to local warming than those born at 29-36 wk at 24, 72, and 120 h of age. Sex-specific differences in microvascular blood flow and vasodilatory capacity in the immediate newborn period may affect the transitional circulation, contributing to excess of morbidity and mortality in preterm males.     

Postnatal changes in intracranial blood flow velocity in preterm infants

Postnatal changes in intracranial arterial blood flow velocity, were studied in preterm infants of less than 34 weeks of gestation. The blood flow velocity was measured in an artery on the base of the skull, using a range-gated Doppler ultrasound velocimeter. Ten healthy infants (mean gestational age 32.5 weeks), and ten infants with transitional respiratory disease (mean gestational age 31.3 weeks) were studied at 1, 2, 5, 24 h, and 2, 3, 5 and 10 days after birth. The healthy infants showed a consistent pattern of changes on the first day, with an average reduction in mean flow velocity of 29% between 1 and 5 h. At 24 h after birth, mean flow velocity had almost returned to the level of the 1 h recording. After 24 h there was a gradual increase in systolic and mean flow velocity until 10 days, while diastolic flow velocity remained unchanged. In the infants with respiratory disease there were no systematic changes in mean flow velocity on the first day, although large individual changes were seen. After 24 h no differences were seen between the healthy infants and the infants with respiratory disease. These findings indicate a transient decrease in cerebral perfusion during early circulatory transition in healthy preterm infants, and that mild to moderate respiratory disease causes larger individual variations in intracranial blood flow velocity.     

����������Ĺ��ܸı����Ѫ��Ӱ����о�

目的 探讨心功能改变对早产儿早期脑血流的影响.方法 2007年1-7月在暨南大学第二附属医院深圳市人民医院新生儿科住院的261例胎龄为29～36+6周的早产儿于生后不同日龄根据左心室射血分数(EF)各分为3组.应用经颅多普勒监测早产儿生后1、3、7 d的大脑中动脉血流速度指标及血管弹性指标.应用彩色多普勒超声心动图监测早产儿心功能指标及主动脉瓣口峰值流速.记录生后1 d早产儿胎龄及出生体重,并监测体温、血气、血糖、血压及红细胞比积.结果 生后1、3、7 d早产儿的脑血流速度均随EF增加而加快;EF与大脑中动脉收缩期峰值流速、舒张期末血流速度、平均血流速度均呈正相关(r分别为0.70、0.41、0.61,P均<0.01),而EF与血管阻力指数及弹性指数未见明显相关性.结论 早产儿早期脑血流速度受左室泵血功能的影响,而胎龄及出生体重是影响早产儿早期左室泵血功能的重要因素.     

Effective pulmonary blood flow in preterm and light-for-date infants.

Using a method employing low concentrations (3%) of nitrous oxide, we measured effective pulmonary capillary blood flow (Qpc eff) in 23 preterm infants, 26 light-for-date infants, and 15 infants who were both preterm and light-for-date. All infants studied had no clinical or laboratory evidence of idiopathic respiratory distress syndrome (IRDS) and were studied before the age of 48 hours. The mean Qpc eff of 175 ml/kg/min in preterm infants (a group at high risk of developing IRDS), although significantly less than the mean of 214 ml/kg/min found in light-for-date infants (a group with a low risk of developing IRDS), was similar to that reported in normal term infants. The mean result for preterm, light-for-date infants was 189 ml/kg/min. No evidence was found that preterm infants were predisposed to IRDS as a consequence of preexisting pulmonary hypoperfusion.     

Aminophylline therapy and cerebral blood flow velocity in preterm infants

Pulsed Doppler ultrasound was used to evaluate the cerebral blood flow velocity (CBFV), in the middle and anterior cerebral arteries in 10 infants before and after the administration of aminophylline (7.5 mg/kg). Mean CBFV, heart rate, blood pressure, oxygen and carbon dioxide tensions were recorded before the loading dose, and then at 1, 2, 6 and 24 h after completion of the infusion. Mean CBFV in the middle and anterior cerebral arteries were 16.8 cm/s and 10.8 cm/s respectively prior to the infusion. There was a significant decrease ( P <0.05) in velocities in both arteries at 1 and 2 h post drug therapy, which returned to base values by 6h, and remained as such at 24h. The heart rate increased ( P <0.05) after the infusion, while no consistent changes were observed in blood pressure or oxygen tension. Carbon dioxide levels were significantly reduced ( P <0.05) at 2h. The reduction in CBFV, however, was more than would be expected on the basis of the change in carbon dioxide levels alone, suggesting that other factors may be exerting an influence. While no adverse effects were noted in the infants studied, it is suggested that aminophyiline should be used judiciously in sick preterm infants at highest risk from ischaemic brain injury.     

Skin blood flow changes during apneic spells in preterm infants

Changes in skin blood flow during apneic spells were determined in 18 preterm infants using a diode laser Doppler flow meter without light conducting fibres. Heart rate, nasal air flow, impedance pneumography, skin and incubator temperature and laser Doppler skin blood flow were recorded simultaneously in each infant. During 212 apneic spells with a duration of 11.6 ± 7.5 s (mean ± S.D.) (range 6.0–48.0 s), the laser Doppler skin blood flow was measured. In all children except one, the majority of the apneic spells was associated with a decrease in skin blood flow. During 155 apneic spells (73%) skin blood flow decreased significantly P < 0.025), the maximum decrease being 16.7 ± 14.8%, 28.5 ± 23.9% and 18.9 ± 16.1% (mean ± S.D.) for central, obstructive and mixed apneic spells, respectively. The decrease in skin blood flow started immediately after the beginning of apneic spells in 71%, the rest started with a mean delay of 3.4 s (range 0.1–7.0 s). No relation was found between the decrease in skin blood flow and the duration of the apneic spells. Thirty-four percent of the apneic spells were accompanied by bradycardia. In apneic spells accompanied by bradycardia the decrease in skin blood flow was not related to the fall in heart rate.     

Sleep-walking shifts and cerebral blood flow in stable preterm infants

Cerebral blood flow was estimated on 60 occasions in 15 well infants, 29-34 wk of gestational age, 5-17 days after birth, using 133-Xenon clearance after intravenous injection. The sleep state of the infants was determined by biparietal electroencephalography, clinical observation, and tracings of heart rate and respiration. Blood flow was 22% higher in the 11 estimations made during wakefulness, when compared to the 17 estimations made during quiet sleep. There was no difference between blood flow in active and quiet sleep. Also there was no difference between blood flow during periods of trace alternant and blood flow during periods of continuous electroencephalographic activity. It is suggested that flow-metabolism coupling is present in stable, preterm infants. The absence of an increase in cerebral blood flow during active sleep as compared with quiet sleep suggests that the neurophysiologic and neurometabolic mechanisms of rapid eye movement sleep are not yet fully developed in preterm infants.