Elevated levels of fetal hemoglobin synthesis in infants with bronchopulmonary dysplasia.

A study was devised to determine whether levels of fetal hemoglobin (HbF) synthesis are elevated in infants with bronchopulmonary dysplasia (BPD) when compared with the levels of HbF synthesis found in normal control infants. Twelve infants with BPD, whose postconceptional ages ranged from 40 to 62 weeks, were studied. The mean (+/- SD) gestational age and birth weight was 29 +/- 1.9 weeks and 1289 +/- 376 g, respectively. Elevation infants matched for birth weight, gestational age, and postnatal age served as the control subjects. Blood samples were incubated in an amino acid mixture containing [14C]leucine. The adult hemoglobin and HbF were then separated by column chromatography on diethylaminoethyl-Sephadex. The results demonstrated that the mean (+/- SD) level of HbF synthesis in infants with BPD was significantly higher than that in the control infants (42.6 +/- 22.9% vs 18.8 +/- 12.8%; P less than .01). When levels of HbF synthesis in the infants with BPD and the control infants were compared with data previously reported in normal infants, 7 of the 12 infants with BPD, but none of the control infants, were synthesizing amounts of HbF greater than would be expected for their postconceptional age. The results suggest that cardiopulmonary insufficiency could stimulate HbF synthesis during the first year of life as a result of an erythropoietic response to hypoxemia.     

Red cell oxygen affinity, hemoglobin type, 2,3-diphosphoglycerate, and pH as a function of fetal development.

Studies were carried out on fresh cord blood obtained at delivery from nonstressed normal fetuses ranging from 24 to 42 weeks of gestation, to determine the relationship of 2,3-diphosphoglycerate (DPG), the intracellular red cell and extracellular pH, and the proportions of adult and fetal hemoglobin in regulating the position of fetal red cell oxygen affinity in utero. There was a significant positive correlation between P50 and gestational age (r = .62, P less than .001), the linear regression increased from 17.8 to 22.5 mm Hg. There was also a significant positive correlation between P50 and the percentage of adult type hemoglobin (HbA) (r = .67, P less than .001). In contrast gestational age had no effect of 2,3-DPG levels, the mean and SD was 14.86 +/- 2.04 mol/gm of Hb or delta pH between plasma and red cell, the mean was 0.187 +/- SD 0.032. However, there was a significant negative correlation between the intraerythrocyte hydrogen ion concentration and DPG level (r = .5, P less than .025). It is concluded therefore that the decrease in fetal oxygen affinity as gestation progresses is related mainly to the increase in the amount of HbA and the levels of DPG or delta pH between plasma and red cells are not a function of gestational age.     

Oxygen transport in congenital heart disease: influence of fetal hemoglobin, red cell pH, and 2,3-diphosphoglycerate.

In 48 individuals (age 1 day to 13 years) with congenital heart disease, blood oxygen transport function was studied in order to evaluate adaptive changes in shunt hypoxemia and to investigate the in vivo regulation of erythrocyte 2, 3-diphosphoglycerate concentration (RBC 2, 3-DPG) in the presence of fetal hemoglobin (HbF). Arterial pO2 and oxygen content, oxygen capacity, acid base status, oxygen affinity, HbF fraction, plasma pH, red cell pH, and RBC 2, 3-DPG were determined. During the first 50 days of life values of standard P50 (stdP50) (37, pH 7.4), actual in vivo P50 (actP50), RBC 2, 3-DPG, O2 capacity, arterial plasma pH, and red cell pH were scattered around the normal range, although tending to low values for stdP50 and arterial plasma pH and to high values for O2 capacity. After the third month, stdP50 actP50, RBC 2, 3-DPG, O2 capacity, and red cell pH were found to be elevated. Plasma pH and actP50 were scattered around the normal range (Figs. 1 and 2). Intraerythrocytic pH in hypoxemic infants was increased compared with normal children when related to plasma pH (Fig. 3). A close to normal intraerythrocytic pH was therefore found in the hypoxemic infants with low plasma pH, and an increased intraerythrocytic pH in the hypoxemic children with normal plasma pH (Fig. 1). A significant negative correlation exists between erythrocyte H+ ion and 2, 3-DPG concentration (Fig. 5); regression constants derived from data at high (mean 47%) and low (mean 9%) fractions of HbF are not significantly different (Regression Equations 8 and 11 in Table 1). Thus, the known difference in 2, 3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2, 3-DPG concentration, indicating that in vivo the 2, 3-DPG synthesis in hypoxia is virtually regulated by the erythrocyte pH, which in turn is determined by plasma pH and the oxygenation state of hemoglobin.     

Cardiopulmonary effects of nebulized sodium nitroprusside in term infants with hypoxic respiratory failure

OBJECTIVE: To study whether nebulized nitroprusside (neb-NP) improves oxygenation in term infants with hypoxic respiratory failure (HRF). STUDY DESIGN: We studied 22 newborn term infants (gestational age, 39.7+/-0.4 weeks [mean+/-SEM]; birth weight, 3.6+/-0.1 kg) with hypoxia (Pao2<100 mm Hg) during mechanical ventilation (Fio2=1.0). Sodium nitroprusside (5 mg followed by 25 mg) was nebulized into the inspiratory arm of the ventilator circuit. Vital signs and arterial blood gas values were recorded after 20 minutes at each dose and before and after initiation of inhaled nitric oxide (iNO). RESULTS: Pao2 increased significantly with 5 mg neb-NP (from 64.6+/-5.6 to 90.1+/-15.3 mm Hg, P=.04) and with 25 mg neb-NP (113.2+/-20.4 mm Hg, P=.009). Differences between mean Pao2 at 5 mg versus 25 mg neb-NP were also statistically significant (P=.03). When comparing the effect of neb-NP to iNO, the treatment-induced increases in Pao2 were similar (52.1+/-18.7 vs 62.2+/-18.2 mm Hg, respectively, P=not significant). CONCLUSIONS: Neb-NP causes a dose-dependent increase in oxygenation in term infants with HRF, similar in magnitude to iNO* Neb-NP may be beneficial in infants with HRF when iNO is not readily available.     

In vitro effects of inosine-pyruvate-phosphate on P50 values and DPG contents of fresh and stored blood from healthy neonates, symptom-free premature infants and premature infants with respiratory distress syndrome.

A study was made of the effect of a 3-hour incubation with inosine-pyruvate-phosphate (IPP) on the P50 values and 2,3-DPG contents of fresh blood and blood which had stood for 96 h, from healthy adults, term neonates, 1-2-week-old symptom-free premature infants and RDS premature infants. It was found that the P50 value and the 2,3-DPG content could be increased considerably by IPP treatment in both the fresh and the stood blood in the various groups of neonates. The question remains open as to whether the effect of IPP, in significantly improving the O2 transport in neonates, is a consequence of the 2,3-DPG alone or of some other metabolite. In RDS the stimulating effect of the IPP mixture is appreciably lower.     

Lower concentration of pulmonary hepatocyte growth factor is associated with more severe lung disease in preterm infants

OBJECTIVES: Hepatocyte growth factor (HGF) participates in normal lung development and in regeneration after lung injury in animals. We studied the role of HGF during the perinatal period and in the development of bronchopulmonary dysplasia (BPD). STUDY DESIGN: HGF was measured in 172 tracheal aspirate fluid samples (TAF) from 17 preterm infants in whom BPD subsequently developed (gestational age, 27.2+/-1.7 weeks; body weight, 828+/-210 g) and from 15 who survived without BPD (gestational age, 26.8+/-1.9 weeks; body weight, 994+/-265 g) during the first 2 postnatal weeks. RESULTS: Infants with subsequent development of BPD had lower HGF in TAF (45+/-9 pg/mL per IgA-sc) than those surviving without BPD (102+/-32 pg/mL per IgA-sc; P=.028). Lower HGF in TAF were seen in infants with more severe acute respiratory distress as defined as requirement for surfactant therapy (50+/-14 vs 146+/-50 pg/mL per IgA-sc in infants requiring no surfactant; P=.0001), for higher number of surfactant doses (r=-0.16, P=.06), and for mechanical ventilation >1 week (167+/-51 vs 51+/-14 pg/mL per IgA-sc in infants intubated <1 week; P=.0012). CONCLUSIONS: These data show an association between lower HGF concentration in TAF and more severe lung disease in human preterm infants in the early neonatal period.     

Deletion allele of angiotensin-converting enzyme is associated with increased risk and severity of bronchopulmonary dysplasia

OBJECTIVE: To explore whether the deletion (D) allele of angiotensin-converting enzyme (ACE) is associated with the risk or severity of bronchopulmonary dysplasia (BPD) among very low birth weight (BW) infants. STUDY DESIGN: Infants with a BW < or = 1250 g were prospectively recruited. The D and I (insertion) alleles of ACE were determined using a polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: Infants with DD/DI genotype of ACE had a (mean +/- SD) birth weight (938 +/- 204 g vs 925 +/- 196 g) and gestational age (28 +/- 3 weeks vs 28 +/- 2 weeks), similar to infants with II genotype of ACE (P > .05). Infants with DD/DI genotype of ACE were more likely to have BPD than infants with II genotype (47% vs 22%, P = .025). Among infants with BPD, ACE DD/DI genotype was more common among infants with moderate or severe BPD compared with infants with mild BPD (74% vs 26%, P = .012). The number of D alleles of ACE correlated directly and positively with the severity of BPD (R = 0.23, P = .045). CONCLUSION: The D allele of ACE is associated with an increased risk and severity of BPD among preterm infants.     

Predictive power of initial severity of pulmonary disease for subsequent development of bronchopulmonary dysplasia

Using retrospectively acquired data from 138 mechanically ventilated premature infants, logistic regression was used to determine the relationships between the risk of bronchopulmonary dysplasia (BPD) and indices of initial respiratory disease severity [oxygen index (OI) and alveolar-arterial pO(2) difference (A-a DO(2))]. Indices were calculated from the first arterial blood gas analysis after initial surfactant administration. Infants were also classified as having mild [OI <4 cm H(2)O x mm Hg(-1), A-a DO(2) <150 mm Hg (20 kPa)] or severe [OI >or=10 cm H(2)O x mm Hg(-1), A-a DO(2) >or=300 mm Hg (40 kPa)] respiratory disease, and the ability of this classification to predict subsequent BPD risk was calculated. OI and A-a DO(2) were significantly higher in the BPD group. Logistic regression analysis showed that BPD risk increased linearly with both OI (9%/cm H(2)O x mm Hg(-1)) and A-a DO(2) [16%/50 mm Hg (16%/6.7 kPa)]. However, the predictive power (receiver-operator characteristic) of these models was modest. Unexpectedly, 29% of infants with mild initial disease developed BPD. These data suggest that, while BPD prediction in infants with severe disease is straightforward, the identification of those few infants with mild to moderate disease destined to develop BPD remains problematic.     

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.     

Oxygen desaturation complicates feeding in infants with bronchopulmonary dysplasia after discharge.

Recurrent episodes of hypoxemia may affect the growth, cardiac function, neurologic outcome, and survival of infants with bronchopulmonary dysplasia (BPD). As oral feeding might stress these infants by compromising pulmonary function even after hospital discharge, we measured oxygen saturation (SaO2) via pulse oximetry before, during the initial 10 minutes of, and immediately after oral feeding in 11 patients with BPD, 12 very low birth weight infants, and 23 healthy full-term infants. All infants with BPD had been previously discharged from the hospital after weaning from supplemental oxygen. Studies were done at a mean postconceptional age of 43 weeks while the infants were fed at home by one of their parents. Levels of SaO2 for the three groups were comparable before and during feeds. After feeding, the infants with BPD had significantly lower mean levels of SaO2 (84 +/- 8% [SD] vs 93 +/- 4% and 93 +/- 3%, respectively; P less than .01). They also spent more time after feeding with an SaO2 less than 90% (64 +/- 34% of time vs 27 +/- 33% for the very low birth weight and 22 +/- 20% for the term group; P less than .01) and greater time with an SaO2 less than 80% (37 +/- 28% vs 4 +/- 10% and 4 +/- 8%, respectively; P less than .01). Desaturation in infants with BPD was related to larger volume and faster oral intake during feeding. Thus, the data indicate that desaturation after feeding remains a recurrent problem for survivors of BPD after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of erythropoietin and its effects on blood lactate and 2, 3-diphosphoglycerate in premature neonates

The aim of this study was to investigate the effect of recombinant human erythropoietin (rHu-EPO) on oxygen affinity and adequate oxygen delivery to the tissues of stable premature infants. 36 very-low-birth-weight infants were randomly assigned to either receive rHu-EPO (200 units/kg every other day) or not, and both groups were supplemented with iron, folic acid and vitamin E. Arterial blood gases, oxygen saturation, complete blood counts, fetal haemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and blood lactate were analysed weekly, from the 1st week till discharge. Patients in the two groups were comparable. There was a trend in increasing lactate values towards the 4th to 5th weeks of life, which did not reach statistical significance. There was no correlation between lactate values and the studied variables (pH, BE, oxygen saturation). In 35 transfusions, pre- and 24 h post-transfusion blood lactate status was studied. In 23 of them, a decrease in post-transfusion lactate was noticed, whilst an increased post-transfusion level was shown in 10 cases and no change in 2 cases. The mean pre-transfusion lactate value was significantly higher than the post-transfusion one (24.04 +/- 11.9 mg/dl before and 16.27 +/- 8.5 mg/dl after transfusion; p = 0.0025). In both groups there was a steady rise in 2,3-DPG concentration over the period of study, and the 2,3-DPG values at the end of our study were significantly increased in the rHu-EPO group (rHu-EPO 5.98 +/- 0.9, control 4.84 +/- 0.7; p = 0.04). In conclusion, the use of rHu-EPO did not affect blood lactate levels compared to the control group. Regarding oxygen affinity, it seems that rHu-EPO causes a shift of the oxy-haemoglobin dissociation curve to the right. This is a previously unreported effect of rHu-EPO and its clinical use may, thus, confer to preterm babies an added advantage.     

Upper- vs lower-limb systolic blood pressure in full-term normal newborns

The difference between upper- vs lower-limb systolic blood pressure (BP) was investigated in 100 normal full-term newborns younger than 24 hours of age by the oscillometric method. The mean systolic BP of both upper limbs was 72.3 +/- 7.6 mm Hg (mean +/- SD). The mean +/- SD systolic BP of both lower limbs was 71.3 +/- 8.2 mm Hg. Systolic BP in the upper limb was greater than that in the lower limb in 66% of newborns by as much as 20 mm Hg (mean +/- SD, 3.5 +/- 3.1). Systolic upper-limb BP was lower than systolic lower-limb BP in 28% of newborns by as much as 21 mm Hg (mean +/- SD, 5.1 +/- 5.1). Systolic BP did not correlate with birth weight. Follow-up evaluation of BP in 25 of the infants up to 3 years of age revealed higher systolic BP in the lower extremities in 24 of the 25 infants. We conclude that (1) it is normal to have a higher systolic BP in either the upper limb or the lower limb in newborns younger than 24 hours of age, and (2) there is no correlation of systolic BP with birth weight in full-term normal neonates younger than 24 hours of age.     

Hypoxic and hypercapneic arousal responses and prediction of subsequent apnea in apnea of infancy

Hypoxic and hypercapneic arousal responses from quiet sleep were tested in 56 infants with apnea of infancy (one or more episodes of cyanosis, limpness, and apnea requiring vigorous stimulation or resuscitation with no treatable cause; age 6.8 +/- 1.1 [SEM] months). Responses were compared with those of nine control infants ranging from 1 to 25 months of age. To assess hypercapneic arousal, the inspired PCO2 was rapidly increased during quiet sleep to 60 mm Hg or until arousal (restlessness, agitation, eye opening) occurred. All control infants and those with apnea of infancy aroused to hypercapnea, but control infants aroused at a lower inspired PCO2 (inspired PCO2 40.1 +/- 2.6 mm Hg) than those with apnea of infancy (inspired PCO2 46.9 +/- 1.5 mm Hg, P less than .05). To assess hypoxic arousal, the inspired PO2 was rapidly decreased during quiet sleep to 80 mm Hg or until arousal occurred. All control infants aroused to hypoxia (inspired PO2 78.3 +/- 2.1 mm Hg). However, only 38% of those with apnea of infancy aroused (inspired PO2 78.1 +/- 0.8 mm Hg), indicating an abnormality in recognition of hypoxia, or central brainstem response to hypoxia. During the 10.4 +/- 1.2 months of follow-up, there was a high incidence of subsequent apneas (greater than 20 seconds) during sleep at home in 50 apneic infants. Infants with abnormal hypoxic arousal responses had more severe subsequent apneas than those with normal hypoxic arousal responses (P less than .05).     

Perinatal changes of 2,3-diphosphoglycerate and oxygen affinity in mammals not having fetal type hemoglobins.

The interrelationship of 2,3-diphosphoglycerate (2,3-DPG) and P50 levels during the fetal and postnatal life were determined in two mammalian species which do not have a switchover of hemoglobin type at the end of their fetal development. In the guinea pig and rabbit, the 2,3-DPG levels remain low during fetal life and increase only after birth remaining elevated throughout adult life. The adult levels were reached at 2 days of age in the guinea pig and the 20th day in rabbit. Fetal P50 values increased only after birth, paralleling the rise in the 2,3-DPG. The rapidity of the postnatal rise in 2,3-DPG and decrease in P50 appears related to the maturity of the newborn animal at birth in these species.     

Hemoglobin-oxygen affinity in hypophosphatemic rickets.

In 14 patients with simple X-linked hypophosphatemic rickets, 5 were below the third percentile in height and 9 were between the third and twenty-fifth percentile. Although the mean serum inorganic phosphorus level was only 2.01 +/- 0.65 (normal range for all age groups is 3.8 to 6.0 mg/100 ml), both the mean values for red cell 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were normal at 4.78 +/- 1.23 and 1.02 +/- 0.17 mumol/ml of red blood cells respectively. Moreover, the mean P50 value was normal at 26.4 +/- 0.9 mmHg. These normal oxygen transport data make unlikely any proposal that short stature seen in these patients is secondary to chronic tissue hypoxia. They also indicate that the intra-erythrocytic organic phosphate levels are maintained at normal levels despite profound chronic hypophosphatemia.     

Apnea of prematurity: I. Lung function and regulation of breathing

It has been suggested that apnea of prematurity may be caused by "immaturity" of central control of breathing. To test the validity of this hypothesis tidal volume (VT), alveolar ventilation (VA), alveolar Pco2 (Paco2), esophageal pressure change, and the slope of the CO2 response curve (delta Ve [minute ventilation]/delta Paco2) were determined in 18 infants with apnea (mean of 32 episodes of more than 20 seconds duration per day) and in 18 healthy newborns used as control subjects. The infants were matched for birth weight (1,068 g v 1,065 g), gestational age (30.2 weeks v 30.2 weeks), and postnatal age (8.6 days v 8.3 days). The results were as follows: Vt (4.4 +/- 1.0 mL/kg v 5.3 +/- 1.6 mL/kg), Va (96 +/- 21 mL/kg/min v 129 +/- 33 mL/kg/min), Paco2 (45.4 +/- 8.5 mm Hg v 35.6 +/- 4.7 mm Hg), esophageal pressure change (4.5 +/- 0.9 cm H2O v 6.0 +/- 1.8 cm H2O), delta Ve/delta Paco2 (20.2 +/- 10.6 mL/min/kg/mm Hg CO2 v 40.7 +/- 19.9 mL/min/kg/mm Hg CO2). There was a significant difference between infants with and without apnea for all measurements. The results indicate a decreased respiratory center output and a depressed ventilatory response to CO2 in infants with apnea. As there was no difference between the two groups in pulmonary mechanics or oxygenation, the findings support the hypothesis that a central disturbance in regulation of breathing is the cause of apnea in these infants.     

Energy expenditure in premature newborns with bronchopulmonary dysplasia.

Five premature newborns (birth weight, mean +/- SD, 960 +/- 145 g; gestational age 28 +/- 1 weeks) with bronchopulmonary dysplasia (BPD) according to the criteria of Bancalari, and 6 controls (birth weight 1,320 +/- 210 g; gestational age 30 +/- 2 weeks) were studied for energy expenditure (EE) by indirect calorimetry. The measurement of total EE was performed when the intake of the infants in both groups was the same and when the respiratory condition had stabilized (control group: postnatal age 31 +/- 6 days, 1,950 +/- 200 g; BPD group: postnatal age 105 +/- 45, postnatal weight 2,440 +/- 380). The BPD group had a higher VO2 (11.15 vs. 8.04 ml/kg/min, p less than 0.01), VCO2 (9.13 vs. 7.74 ml/kg/min, p less than 0.02) and total EE (76 vs. 61 kcal/kg/day, p less than 0.02). The highest values were encountered in the 3 more severely ill infants: mean VO2 11.03 ml/kg/min, mean EE 82 kcal/kg/min. In these cases, administration of medium chain triglycerides limits the increase in VCO2 and lowers the respiratory quotient (0.87 vs. 0.96 in controls.     

Cerebral blood flow velocity in term newborn infants: changes associated with ductal flow

The effects of ductal closure on range-gated pulsed Doppler cerebral blood flow velocity (CBFV) patterns in the internal carotid, anterior cerebral, and middle cerebral arteries were studied in 10 normal term infants (mean birth weight 3302 +/- 294 g (SD) and mean gestational age 39.6 +/- 1.3 weeks). Pulsatility was calculated from flow velocities and used as an estimate of cerebral blood flow (CBF). Ductal closure was associated with a rise in mean blood pressure from 45.0 +/- 4.2 to 51.3 +/- 6.5 mm Hg (P less than 0.05) and a significant decrease in pulsatility in all three vessels (mean = 0.77 +/- 0.07 vs 0.70 +/- 0.05 (P less than 0.02]. Changes in pulsatility were correlated with changes in mean blood pressure (P less than 0.02), providing evidence that systemic blood pressure may influence postnatal cerebral arterial pulsatility indices. We also noted significant differences in the velocity and pulsatility of individual vessels that were independent of blood pressure, suggesting that Doppler flow studies may be useful in describing regional CBF patterns. The temporal association between ductal closure and decreased pulsatility suggests that CBFV patterns reflect ductal shunting in normal term newborn infants. Diastolic runoff and reduced systemic blood pressure in the presence of ductal shunting appear to reduce diastolic flow velocity and increase CBFV pulsatility in normal term infants during the first days of life. Normal mechanisms of cerebral autoregulation compensate for decreased flow with vasodilation; therefore the increased pulsatility associated with ductal shunting may be due to diastolic runoff rather than increased cerebrovascular resistance.     

Outcome of extremely preterm infants randomized at birth to different PaCO2 targets during the first seven days of life

BACKGROUND: Ventilation with higher PaCO(2) goals may reduce lung injury and bronchopulmonary dysplasia (BPD). The effect may be enhanced by using a higher PaCO(2) goal than in previous trials. OBJECTIVE: To determine the clinical benefits and safety of higher PaCO(2) goals for ventilated preterm infants. STUDY DESIGN: Preterm infants with a gestational age between 23 and 28 completed weeks receiving mechanical ventilation within 6 h of birth were randomized to be managed with either a PaCO(2) target between 55 and 65 mm Hg (7.3- 8.7 kPa, minimal ventilation) or 35 and 45 mm Hg (4.7- 6.0 kPa, routine ventilation) for the first 7 days of life. The primary outcome measure was BPD, defined as need for mechanical ventilation or supplemental oxygen at 36 weeks postmenstrual age, or death. The neurodevelopmental status was assessed at 18-22 months corrected age. RESULTS: The trial was stopped early after enrolling 31% of the projected sample size. Enrolled infants had a median birth weight of 640 g. BPD or death occurred in 21/33 (64%) infants after minimal ventilation and 19/32 (59%) infants after routine ventilation. Minimal ventilation was associated with trends towards higher mortality and higher incidence of neurodevelopmental impairment, and a significantly increased combined outcome of mental impairment or death (p < 0.05). CONCLUSION: Minimal ventilation as performed in this study did not improve clinical outcome, and may have been associated with a worse neurodevelopmental outcome.     

Blood volume assessment with hemoglobin subtype analysis in preterm infants

The aim of the study was to assess plasma volume (PV) and red cell volume (RCV) in preterm infants with a liquid chromatographic hemoglobin subtype method (HbST) based on dilution of autologous fetal hemoglobin (HbF) by donor adult hemoglobin and measurement of the amount of HbF. PV determination with the indocyanine green dye dilution technique (ICG) was used as a reference method. Eight infants, median gestational age 29.8 weeks (range 27.6-30.9 weeks) and median birth weight 1,300 g (range 1,030-1,760 g), were studied at a median age of 3.0 days (range 1-6 days). RCV was 33.6 +/- 12 ml/kg measured with ICG and 32.1 +/- 5.2 ml/kg with HbST. PV was 47.0 +/- 18 and 40.2 +/- 6.6 ml/kg, respectively. There was a close correlation between the RCVs measured with the two techniques (Pearson correlation 0.83, p < 0.05). In conclusion, HbST provides a reliable and safe determination of RCV in preterm infants.