Oxygen-saturation targets and outcomes in extremely preterm infants. Patterns of physiologic and behavioral response of intermediate care preterm infants to intervention. Randomized controlled trial of very early continuous distending pressure in the management of preterm infants. A double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses. [Is oxygen therapy truly useful and necessary during elective cesarean section under spinal anesthesia?]. Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates. Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia. Effect of early initiation of intravenous lipid administration on the incidence and severity of chronic lung disease in premature infants. Inhaled nitric oxide in the management of preterm infants with severe respiratory failure.
Physiological studies have shown that chronic hypoxemia may occur in preterm infants who require supplemental oxygen for extended periods and that this hypoxemia may contribute to poor growth and development. Anecdotal reports and uncontrolled observational studies have suggested that a higher oxygen-saturation range may be beneficial in terms of growth and development.
                We conducted a multicenter, double-blind, randomized, controlled trial involving 358 infants born at less than 30 weeks of gestation who remained dependent on supplemental oxygen at 32 weeks of postmenstrual age. They were randomly assigned to a target functional oxygen-saturation range of either 91 to 94 percent (standard-saturation group) or 95 to 98 percent (high-saturation group); this target was maintained for the duration of supplemental-oxygen therapy. The primary outcomes were growth and neurodevelopmental measures at a corrected age of 12 months.
                There were no significant differences between the groups in weight, length, or head circumference at a corrected age of 12 months. The frequency of major developmental abnormalities also did not differ significantly between the standard-saturation group and the high-saturation group (24 percent and 23 percent, respectively, P=0.85). There were six deaths due to pulmonary causes in the high-saturation group and one such death in the standard-saturation group (P=0.12). The high-saturation group received oxygen for a longer period after randomization (median, 40 days vs. 18 days; P<0.001) and had a significantly higher rate of dependence on supplemental oxygen at 36 weeks of postmenstrual age and a significantly higher frequency of home-based oxygen therapy.
                Targeting a higher oxygen-saturation range in extremely preterm infants who were dependent on supplemental oxygen conferred no significant benefit with respect to growth and development and resulted in an increased burden on health services.
                Copyright 2003 Massachusetts Medical Society To determine the safety of a developmental intervention for use with preterm infants and feasibility of a time sampling procedure.
                An experimental design was used to test an intervention with clinically stable 33-34-week postconceptional age infants over a 4-day period. Repeated outcome measures included pulse rate, oxygen saturation levels, and infant behavioral state.
                The intervention resulted in significant differences in infant behavioral state with the experimental group achieving more alertness. Physiologic parameters remained within normal limits both during and after the intervention.
                The protocol was found to be safe for implementation with clinically stable preterm infants. Behavioral state findings suggest the potential for the intervention to promote alertness. Results suggest that changes in oxygen saturation and pulse rate were dependent upon changes in behavioral state. Application of continuous distending pressure at birth (very early CDP) should stabilize the immature airways and reduce the severity of respiratory distress syndrome (RDS) in preterm infants. Eighty-two preterm infants of less than 32 weeks gestation were randomly assigned at birth to early treatment group (TG), in which CDP of 6 cm water pressure was applied at birth by the nasopharyngeal route (NP-CDP), or to control group (CG), in which CDP was applied when indicated for established criteria (pO2 less than 50 mmHg in FiO2 greater than 0.5). Characteristics of the infants in the two groups were comparable. No statistically significant difference between the two groups was found in the incidence of RDS. The course of RDS, and oxygen and ventilatory requirements also did not appear to be changed. In blood gas parameters of most of the time frames, no significant difference was found between the two groups when the results were analyzed according to the assigned group. When the results were analyzed separately for the infants who developed RDS, infants in TG appear to have fared worse from the therapy in terms of oxygenation, as indicated by significantly higher FiO2 (P less than 0.01) and lower a/A (P less than 0.01) values on the third day of the course of RDS, as compared to infants in CG. The incidence of complications was comparable in the two groups. Four infants from TG (9.3%) and one from CG (2.6%) died (P = NS). We conclude that VECDP by nasopharyngeal route does not reduce the incidence of RDS and does not appear to improve the outcome and may worsen the severity of RDS when compared to application of CDP for established criteria. To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation.
                A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air.
                A tertiary referral hospital in South Africa.
                Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery.
                After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet.
                Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero.
                There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days).
                This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients. To analyze maternal and fetal well-being with and without the application of oxygen therapy.
                Randomized trial of full-term parturients who had received prenatal care during pregnancy. The women were healthy and classified as ASA 1. They were scheduled for delivery by cesarean section under spinal anesthesia and randomized to 2 groups to breathe room air or air providing an inspired oxygen fraction of 40% through a face mask. We assessed the well-being of the neonate immediately after birth with the Apgar test and by measuring umbilical cord blood gases.
                One hundred thirty women were enrolled. Both groups were similar, with no differences in demographic or hemodynamic variables, time from uterine incision to fetal extraction, neonatal birth weight, presence of umbilical cord abnormalities, type of resuscitation required by the neonate, or Apgar score in the first or fifth minute. Oxygen saturation in maternal blood by pulse oximetry was higher after 10 minutes in the group of women who received supplemental oxygen through face masks. We also observed significant differences in umbilical cord arterial blood between the room air and supplemental oxygen groups, respectively, as follows: PaCO2, 51.14 mm Hg vs 54.33 mm Hg (P=.016); bicarbonate, 22.19 mEq L(-1) vs 23.23 mEq L(-1) (P=.012); lactate, 1.85 mmol L(-1) vs 1.64 mmol L(-1) (P=.038). The PO2 in venous blood also differed significantly: 25.53 mm Hg vs 28.13 mm Hg, respectively (P=033).
                Breathing supplemental oxygen or not during elective cesarean delivery of healthy parturients under spinal anesthesia does not have a significant effect on neonatal well-being. Traditionally, asphyxiated newborn infants have been ventilated using 100% oxygen. However, a recent multinational trial has shown that the use of room air was just as efficient as pure oxygen in securing the survival of severely asphyxiated newborn infants. Oxidative stress markers in moderately asphyxiated term newborn infants resuscitated with either 100% oxygen or room air have been studied for the first time in this work.
                Eligible term neonates with perinatal asphyxia were randomly resuscitated with either room air or 100% oxygen. The clinical parameters recorded were those of the Apgar score at 1, 5, and 10 minutes, the time of onset of the first cry, and the time of onset of the sustained pattern of respiration. In addition, reduced and oxidized glutathione concentrations and antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) were determined in blood from the umbilical artery during delivery and in peripheral blood at 72 hours and at 4 weeks' postnatal age.
                Our results show that the room-air resuscitated (RAR) group needed significantly less time to first cry than the group resuscitated with 100% oxygen (1.2 +/- 0.6 minutes vs 1.7 +/- 0.5). Moreover, the RAR group needed less time undergoing ventilation to achieve a sustained respiratory pattern than the group resuscitated with pure oxygen (4.6 +/- 0.7 vs 7.5 +/- 1.8 minutes). The reduced-to-oxidized-glutathione ratio, which is an accurate index of oxidative stress, of the RAR group (53 +/- 9) at 28 days of postnatal life showed no differences with the control nonasphyxiated group (50 +/- 12). However, the reduced-to-oxidized-glutathione ratio of the 100% oxygen-resuscitated group (OxR) (15 +/- 5) was significantly lower and revealed protracted oxidative stress. Furthermore, the activities of superoxide dismutase and catalase in erythrocytes were 69% and 78% higher, respectively, in the OxR group than in the control group at 28 days of postnatal life. Thus, this shows that these antioxidant enzymes, although higher than in controls, could not cope with the ongoing generation of free radicals in the OxR group. However, there were no differences in antioxidant enzyme activities between the RAR group and the control group at this stage.
                There are no apparent clinical disadvantages in using room air for ventilation of asphyxiated neonates rather than 100% oxygen. Furthermore, RAR infants recover more quickly as assessed by Apgar scores, time to the first cry, and the sustained pattern of respiration. In addition, neonates resuscitated with 100% oxygen exhibit biochemical findings reflecting prolonged oxidative stress present even after 4 weeks of postnatal life, which do not appear in the RAR group. Thus, the current accepted recommendations for using 100% oxygen in the resuscitation of asphyxiated newborn infants should be further discussed and investigated. To determine whether long-term oral diuretic therapy would improve the pulmonary function of preterm infants with bronchopulmonary dysplasia.
                Randomized, double-blind, placebo-controlled study.
                Level III intensive care nursery.
                We randomly selected 43 stable patients with oxygen-dependent bronchopulmonary dysplasia to receive either orally administered spironolactone and chlorothiazide or placebo. These drugs were continued until the patients no longer required supplemental oxygen. Both groups received furosemide as needed.
                Each infant had pulmonary function tests at study entry, 4 weeks after study entry, 1 week and 8 weeks after being weaned to room air and off study drugs, and at 1 year of corrected age. Pulmonary function tests include dynamic pulmonary compliance, airway resistance, thoracic gas volume, and maximal expiratory flow at functional residual capacity; most of the infants had functional residual capacity measured. Between the first and second pulmonary function tests (while the infants were receiving diuretic or placebo), the infants in the diuretic group had a significant improvement in dynamic pulmonary compliance (46%; p < 0.001) and airway resistance (31%; p < 0.05); there were no changes in compliance or resistance in the placebo group. Although patients in both the diuretic and the placebo groups required progressively less supplemental oxygen, by 4 weeks after study entry the patients in the diuretic group needed less supplemental oxygen than did those in the placebo group (p < 0.01). There were no significant differences in results of serial pulmonary function tests in either group after discontinuation of diuretic therapy. Despite the significant differences in pulmonary function between the two groups, there was no significant difference between them in the total number of days that supplemental oxygen was required. Significantly more infantsin the placebo group received more than 10 doses of furosemide on an as-needed basis.
                Long-term diuretic therapy in stable infants with oxygen-dependent bronchopulmonary dysplasia, after extubation, improves their pulmonary function and decreases their fractional inspired oxygen requirement, but does not decrease the number of days that they require supplemental oxygen. The improvement in pulmonary function associated with diuretic therapy is not maintained after treatment is discontinued. To investigate whether intravenous administration of lipid nutrition (Intralipid) within 12 hours of birth to ventilator-dependent premature infants would decrease the incidence or severity, or both, of chronic lung disease.
                We randomly assigned 133 infants to Intralipid or control groups, using two weight strata: 42 Intralipid versus 37 control subjects in the 600 to 800 gm stratum, and 28 Intralipid versus 26 control subjects in the 801 to 1000 gm stratum. The Intralipid group received 20% Intralipid at < 12 hours after birth, starting at a dose of 0.5 gm/kg and increasing to a maximum of 1.5 gm/kg, maintained through day 7. Control infants received no lipid until after day 7. Neither group received enteral feedings until after day 7.
                No significant differences in mortality rates were present in the total population (23/70 = 32.9% vs 16/63 = 25.4%; p = 0.35, Intralipid vs control); however, the mortality rate increased significantly in 600 to 800 gm infants receiving Intralipid versus the control infants (20/41 = 47.5% vs 9/37 = 24.3%; p = 0.032). No significant differences were found in the number of infants in whom chronic lung disease developed (requiring oxygen for > or = 28 days), proportion requiring oxygen for > or = 60 days, number of survivors without chronic lung disease, or total oxygen and ventilation requirements. However, 600 to 800 gm infants receiving Intralipid had significantly more pulmonary hemorrhage, and greater numbers of infants receiving Intralipid in both weight categories required supplemental oxygen at day 7. The incidence of other complications of prematurity, time required to regain birth weight, and duration of hospital stay did not differ between groups.
                Intralipid administration initiated at < 12 hours after birth failed to protect very low birth weight premature infants from chronic lung disease. Some of the results raise questions about possible deleterious effects of Intralipid when administered early in the first week of life. Elevated pulmonary vascular resistance and poor ventilation-perfusion matching are commonly found in preterm infants with severe respiratory distress syndrome (RDS) and respiratory failure. Inhaled nitric oxide (iNO) can improve gas exchange and decrease pulmonary vascular resistance. This study was conducted to determine whether iNO therapy improves oxygenation in such infants.
                Between July 2000 and 2006, 65 preterm infants (birth weight, <1500 g; gestational age, <31 weeks) with severe RDS and respiratory failure requiring mechanical ventilation and an oxygenation index (OI)>or=25 were randomly divided into two groups. Group A infants (n=32) received iNO therapy. iNO was started at a dose of five parts per million (p.p.m.). The maximal dose of NO was 20 p.p.m. Group B infants (n=33) did not receive iNO therapy, receive inhaled oxygen placebo only, was served as control group. Mechanical ventilation and iNO therapy were managed by neonatologists who were not involved in safety monitoring, data analysis and interpretation, or manuscript preparation. This study was randomized but not blinded.
                The OI was significantly lower (P<0.01) in the iNO therapy group than in the control group at 30 min, 3, 12 and 24 h after initiating iNO therapy. Six infants in the iNO-treated group and 10 infants in the control group died. Post hoc analyses did not reveal any significant differences in the incidences of chronic lung disease (CLD), intracranial hemorrhage (ICH), patent ductus arteriosus (PDA), retinopathy of prematurity (ROP) or duration of intubation between the iNO-treated and the control groups.
                We conclude that iNO therapy leads to an improvement in oxygenation without short-term side effects (such as pulmonary hemorrhage, intracranial hemorrhage, pneumothorax or acute deterioration) in premature infants with severe RDS and respiratory failure. However, iNO therapy does not significantly reduce mortality rate or the incidences of CLD, ICH, PDA or ROP.
The results of this systematic review confirm that (the now historical) policy of unrestricted, unmonitored oxygen therapy has potential harms without clear benefits. However, the question of what is the optimal target range for maintaining blood oxygen levels in preterm/LBW infants was not answered by the data available for inclusion in this review.