Antenatal betamethasone treatment has a persisting influence on infant HPA axis regulation.

OBJECTIVE: To examine the consequences of antenatal betamethasone (AB) exposure on postnatal stress regulation. STUDY DESIGN: Fourteen AB exposed infants born at 28-30 weeks' gestation were assessed in the NICU during postnatal week 1 and at 34 weeks postconception. Nine infants born at 34 weeks gestation without AB treatment were evaluated as a postconceptional age comparison group. Salivary cortisol, heart rate, and behavior were measured at baseline and in response to a heelstick blood draw. RESULTS: Repeated measures ANOVAs revealed that both groups displayed an increase in heart rate and behavioral distress in response to the stressor. The cortisol response, however, was blunted in AB-treated infants at both assessments. CONCLUSION: AB treatment has consequences for hypothalamic-pituitary-adrenal (HPA) axis regulation that persist for at least four to six weeks after birth, indicating that studies of long-term effects are warranted.

Randomized, controlled trial of low-dose inhaled nitric oxide in the treatment of term and near-term infants with respiratory failure and pulmonary hypertension.

UNLABELLED: Recent reports indicate that inhaled nitric oxide (iNO) causes selective pulmonary vasodilation, increases arterial oxygen tension, and may decrease the use of extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). Despite these reports, the optimal dose and timing of iNO administration in PPHN remains unclear. OBJECTIVES: To test the hypotheses that in PPHN 1) iNO at 2 parts per million (ppm) is effective at acutely increasing oxygenation as measured by oxygenation index (OI); 2) early use of 2 ppm of iNO is more effective than control (0 ppm) in preventing clinical deterioration and need for iNO at 20 ppm; and 3) for those infants who fail the initial treatment protocol (0 or 2 ppm) iNO at 20 ppm is effective at acutely decreasing OI. STUDY DESIGN: A randomized, controlled trial of iNO in 3 nurseries in a single metropolitan area. Thirty-eight children, average gestational age of 37.3 weeks and average age <1 day were enrolled. Thirty-five of 38 infants had echocardiographic evidence of pulmonary hypertension. On enrollment, median OI in the control group, iNO at 0 ppm, (n = 23) was 33.1, compared with 36.9 in the 2-ppm iNO group (n = 15). RESULTS: Initial treatment with iNO at 2 ppm for an average of 1 hour was not associated with a significant decrease in OI. Twenty of 23 (87%) control patients and 14 of 15 (92%) of the low-dose iNO group demonstrated clinical deterioration and were treated with iNO at 20 ppm. In the control group, treatment with iNO at 20 ppm decreased the median OI from 42.6 to 23.8, whereas in the 2-ppm iNO group with a change in iNO from 2 to 20 ppm, the median OI did not change (42.6 to 42.0). Five of 15 patients in the low-dose nitric oxide group required ECMO and 2 died, compared with 7 of 23 requiring ECMO and 5 deaths in the control group. CONCLUSION: In infants with PPHN, iNO 1): at 2 ppm does not acutely improve oxygenation or prevent clinical deterioration, but does attenuate the rate of clinical deterioration; and 2) at 20 ppm acutely improves oxygenation in infants initially treated with 0 ppm, but not in infants previously treated with iNO at 2 ppm. Initial treatment with a subtherapeutic dose of iNO may diminish the clinical response to 20 ppm of iNO and have adverse clinical sequelae.

The relationship between fetal arterial oxygen saturation and heart and skeletal muscle myoglobin concentrations in the ovine fetus.

Myoglobin, a hemoprotein found in abundance in the muscle of postnatal animals, increases in concentration in response to hypoxia, thereby protecting tissue from damage. Fetuses exposed to intrauterine hypoxemia are also susceptible to organ damage, but the response of fetal muscle myoglobin to hypoxemia is unknown. To study whether fetal muscle myoglobin concentrations are elevated following intrauterine hypoxemia, we exposed eight chronically catheterized late gestation sheep to a wide range of fetal oxygen levels over 15 to 30 days and correlated the level of fetal oxygenation with heart and skeletal muscle myoglobin concentrations measured at sacrifice. A lower level of fetal oxygenation, expressed as the integrated area under the arterial saturation (SaO2)-time curve, was associated with greater myocardial myoglobin concentration (r = 0.90; P < 0.01). This relationship was not observed for skeletal muscle (r = 0.43; P = ns). A lower level of fetal oxygenation was associated with lower myoglobin:iron (w/w) ratio in skeletal muscle (r = 0.71; P < 0.03), implying less incorporation of iron into myoglobin. A similar relationship was not apparent for cardiac tissue. The higher myocardial myoglobin concentrations found in the more hypoxic fetuses were consistent with previous observations in postnatal animals. This likely represents an intracellular compensatory mechanism for sustaining short-term mitochondrial oxygen delivery in a critical organ with a high rate of oxygen consumption. The lack of myoglobin responsiveness to hypoxia in fetal skeletal muscle may be due to its much lower oxygen consumption rate and activity level.

Intracardiac iron distribution in newborn guinea pigs following isolated and combined fetal hypoxemia and fetal iron deficiency.

Myocardial iron deficiency complicates chronic intrauterine hypoxemia during diabetic pregnancies. To understand the effect of both conditions during fetal life on intracardiac iron prioritization, we measured heart myoglobin, cytochrome c, and elemental iron concentrations in six iron-deficient, hypoxic, five iron-sufficient, hypoxic, six iron-deficient, normoxic, and six iron-sufficient, normoxic newborn guinea pigs. The iron-deficient, hypoxic group had lower heart iron (p = 0.03) but higher myoglobin concentration (p < 0.0001) when compared with the iron-sufficient, normoxic group. The percentage of iron incorporated into myoglobin was higher than control in the iron-deficient, hypoxic group (23.2+/-7.2% vs. 5.2+/-0.8%; p < 0.001) and increased as total heart iron decreased (r = 0.97; p < 0.001). In contrast, heart cytochrome c concentration was lower than control in the iron-deficient, hypoxic group (p = 0.01), with equal percentages of heart iron incorporated into cytochrome c. This intracellular prioritization of myocardial iron to myoglobin and away from cytochrome c following combined fetal hypoxemia and iron deficiency may represent an adaptive mechanism to preserve myocardial tissue oxygenation, although at the expense of oxidative phosphorylative capability.

Intravenous iron supplementation effect on tissue iron and hemoproteins in chronically phlebotomized lambs.

Chronic phlebotomy is an important mechanism of iron loss in premature infants. We studied inter- and intraorgan iron allocation in 10 twin lamb pairs undergoing an acute 40-50% reduction in red cell volume followed by smaller intermittent phlebotomies over an 11-day period. One twin received no supplemental iron sucrose, while the other received an average daily intravenous dose of iron sucrose of either 1 (n = 3), 2 (n = 3), 5 (n = 3), or 15 (n = 1) mg.kg-1.day-1. The total iron content of the red blood cells, liver, skeletal muscle, heart, and brain was directly related to iron dose up to 2 mg.kg-1.day-1. Tissue iron concentrations remained stable until liver iron was < 200 g/g dry wt, after which iron was preferentially directed to red blood cells over skeletal muscle, heart, and brain. Hemoprotein concentrations decreased proportionately to tissue iron, except myocardial cytochrome c, which remained preserved. Any available iron in phlebotomized, rapidly growing lambs is preferentially directed to red blood cells, and lambs require iron supplementation to maintain tissue iron and hemoprotein concentrations. A decrease in nonheme tissue iron results in the high prioritization of iron among iron-containing proteins.