High flow nasal cannula versus nasal CPAP for neonatal respiratory disease: a retrospective study.

OBJECTIVE: Our objective is to assess the frequency of usage, safety and clinical utility of humidified high flow nasal cannula (HHFNC) in two tertiary care hospitals and compare outcomes to a historical control group of premature infants who received nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: The first part of the study describes the increased HHFNC usage in two tertiary neonatal intensive care units. The second part compares outcomes of infants, born at less than 30 weeks gestation, who received either NCPAP or HHFNC as an early respiratory support mode. RESULTS: HHFNC usage increased (64%) after its introduction in infants of all gestational ages whereas the usage of NCPAP decreased from 19 to 4%. Ninety-five percent of infants born at less than 30 weeks gestation received HHFNC at some point during their hospital stay whereas only 12% received NCPAP. There were no differences in death or bronchopulmonary dysplasia (BPD), but ventilator-days per patient were decreased (19.4 to 9.9) following introduction of HHFNC. Comparing the cohort of infants who received either NCPAP or HHFNC as an early mode of respiratory support, there were no differences in deaths, ventilator-days, BPD, blood infections or other outcomes. More infants were intubated for failing early NCPAP compared to early HHFNC (40 to 18%). CONCLUSIONS: HHFNC was well-tolerated by premature infants. Compared to infants managed with NCPAP, there were no apparent differences in adverse outcomes following the introduction of HHFNC. Additional research is needed to better define the utility and safety of HHFNC compared to NCPAP.

Fatal carnitine palmitoyltransferase II deficiency in a newborn: new phenotypic features.

We describe the term male infant of asymptomatic, healthy nonconsanguineous parents presenting on the first day of life with nonketotic hypoglycemia, seizures, hepatomegaly, cardiomegaly with biventricular hypertrophy, and ventricular arrhythmias. Cranial ultrasound revealed cystic dysplasia with several foci of hyperechogenicity within the right basal ganglia. Free carnitine was markedly decreased in the urine and plasma with a pronounced elevation of plasma long-chain acylcarnitines. Fibroblast carnitine palmitoyltransferase II activity was reduced to 26% and 38% in the father and mother, respectively. The infant expired on day 5 of life from malignant ventricular tachy-arrhythmias. Diffuse lipid accumulation was evident at autopsy, including in the liver, heart, kidney, adrenal cortex, skeletal muscle, and lungs. This new case of infantile CPT-II deficiency illustrates the severity of the early onset form of CPT-II deficiency.

Inducible nitric oxide synthase and the regulation of central vessel caliber in the fetal rat.

BACKGROUND: The purpose of this study was to evaluate the possibility that inducible nitric oxide synthase (iNOS) regulates the fetal circulation. METHODS AND RESULTS: Positive evidence for iNOS gene expression was noted in heart central vessels and placenta of untreated rat fetuses. Rats in the last week of pregnancy were treated for 5 days with L-NG-(1-Iminoethyl)lysine (L-NIL), a selective inhibitor of iNOS, at 1, 10, and 100 micrograms/mL in the drinking water. To raise NO levels, lipopolysaccharide (LPS) 30 micrograms/kg was given by intraperitoneal injection, and sodium nitroprusside (SNP) was placed in mini-osmotic pumps to deliver 10 micrograms/kg per minute. Control animals were undisturbed. On day 21 of gestation, dams were anesthetized and fetuses were delivered by cesarean section and rapidly frozen in isopentane chilled in liquid nitrogen. Frozen sections (10 microns) were used to reconstruct a computer-generated three-dimensional image of the great vessels and ductus arteriosus. Significant constriction of the great vessels and ductus arteriosus was observed with L-NIL, whereas both LPS and SNP dilated these vessels. The vasorelaxant effect of LPS was blocked by L-NIL. NO release from placental explants was 633 +/- 41 nmol/L under basal conditions, increasing to 4.0 +/- 0.4 mumol/L with LPS administration, although placental iNOS message and protein levels were unchanged. CONCLUSIONS: We suggest that nitric oxide, generated by iNOS, plays a significant role in control of major vessel and ductus arteriosus caliber in the rat fetus. In regard to the nitrergic regulation of the circulation, the fetus is clearly different from the adult.

Fetal growth retardation in rats may result from apoptosis: role of peroxynitrite.

Administration of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) results in fetal growth retardation. This study was designed to further examine the influence of NO on fetal growth, specifically, the potential role of inducible NOS and to evaluate the possibility that apoptosis contributed to uteroplacental dysfunction. L-NAME administration caused a paradoxical increase in NO synthesis determined by direct detection of NO by electrochemistry, nitrite accumulation, and cGMP levels, indicating that a lack of NO was not the cause of the fetal growth retardation. Additionally, supplemental L-arginine or NO donors failed to reverse the effects of L-NAME on fetal and placental size. Administration of low dose endotoxin (30 micrograms/kg IP daily for 6 d) also caused significant reductions in fetal and placental size and increased NO synthesis comparable to that seen with L-NAME. Inducible NOS was constitutively expressed in the pregnant uterus (smooth muscle and epithelia) and placenta (sinusoids and macrophages) but was absent in the nonpregnant state as determined by RT-PCR and immunohistochemistry. Neither L-NAME nor endotoxin modified the expression of iNOS. In situ evidence for apoptosis (DNA fragmentation) was minimal to absent in control pregnant rats, but markedly evident in the placenta (decidua) and uterus of rats treated with L-NAME or endotoxin. Immunohistochemical evidence for nitrotyrosine, a marker for peroxynitrite formation, was absent in control rats but colocalized with apoptosis in the L-NAME and LPS groups. We conclude that L-NAME-induced fetal growth retardation is not due to a lack of NO, but as for endotoxin, results from a net reduction in cellular proliferation due to the induction of apoptosis, possibly in response to peroxynitrite formation.

Limb reduction defects after prenatal inhibition of nitric oxide synthase in rats.

To determine the influence of nitric oxide (NO) on vascular tone during fetal development, timed pregnant rats received the NO synthase inhibitor NG-nitro-L-arginine methyl ester for consecutive 4, 7, or 14 d before parturition (postorganogenesis). Offspring demonstrated limb reduction defects (incidence, 53%) involving either or both hindlimbs, whereas forelimbs were uniformly spared. Defects were dose-dependent but independent of the duration of administration occurring with equal frequency in 4-, 7-, and 14-d treatment groups. Histologic analysis revealed features characteristic of vascular disruption with hemorrhagic necrosis and loss of structure. The defects were prevented by concurrent maternal administration of L-arginine or the NO donors S-nitroso-N-acetyl-penicillamine and sodium nitroprusside. Defects were not seen after prenatal treatment with aminoguanidine. To study basal and agonist-mediated NO release, newborn femoral and brachial arteries were cannulated with a glass micropipette under constant pressure, and changes in intraluminal diameter (micrometers) were measured in response to acetylcholine and the NO synthase inhibitor N omega-nitro-L-arginine. Newborn femoral and brachial vessels demonstrated a dramatic (59%) decrease in resting diameter compared with adult vessels (16%). These findings suggest that basal NO release is upregulated during fetal development concurrent with the processes that increase maternal NO release. The data also suggest that up-regulation of NO release occurs throughout the fetal systemic circulation and is not restricted to hindlimbs. This is the first study to demonstrate inhibition of NO release in the pathogenesis of limb reduction defects.

Perinatal nitric oxide synthase inhibition retards neonatal growth by inducing hypertrophic pyloric stenosis in rats.

Administration of the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) during pregnancy has been shown to compromise fetal growth. This study was designed to determine whether aminoguanidine, a predominate inhibitor of inducible NOS, affects fetal outcome. In addition, we extended the prenatal administration of L-NAME into the postnatal period (14 d) to determine whether neonatal growth and maturation were also affected. L-NAME, but not aminoguanidine, compromises fetal and placental growth. When compared with control 14-d-old pups, postnatal L-NAME compromised neonatal growth, whether it was given directly (intraperitoneally) (39.7 +/- 1.1 versus 24.1 +/- 1.0 g) or indirectly (38.6 +/- 0.5 versus 22.2 +/- 1.2 g) via maternal breast milk. Neonatal growth retardation was asymmetric, with brain sparing, suggesting a nutritional origin. L-NAME administration resulted in growth retardation that extended into adulthood, without evidence of catch-up growth. Treated neonates displayed the hallmarks of hypertrophic pyloric stenosis. Significant increases in stomach weight/pup weight (9.9 +/- 0.3 versus 8.2 +/- 0.4 x 10(3)) and stomach volume/pup weight (12.0 +/- 0.6 versus 9.4 +/- 0.6 mL/100 g) with a concomitant decrease in small intestine weight/length (2.10 +/- 0.08 versus 3.18 +/- 0.13 g/100 cm) was noted in treated versus control pups (p < 0.05). Muscularis hypertrophy at the pyloric sphincter in the L-NAME-treated pups was noted by histology. Blood pressure was elevated in the L-NAME-treated pups (93 +/- 6 versus 60 +/- 5 mm Hg in control pups, p < 0.05). These findings are consistent with inhibition of neuronal and endothelial NOS activity. We conclude that NO, formed via the constitutive isoforms of NOS, is a critical determinant of fetal and neonatal growth and maturation.

Nitric oxide synthase inhibition decreases tolerance to hyperoxia in newborn rats.

We evaluated the effects of sustained perinatal inhibition of NO synthase (NOS) on hyperoxia induced lung injury in newborn rats. N(G)-nitro-Larginine-methyl-ester (L-NAME) or untreated water was administered to pregnant rats for the final 7 days of gestation and during lactation; followed by postnatal exposure to hyperoxia (>95% O(2)) or room air. The survival rate of L-NAME treated pups when placed in > 95% O(2) at birth was significantly lower than controls from day 4 (L-NAME, 87%; control pups, 100%, p < 0.05) to 14 (L-NAME, 0%; control pups, 53%, p < 0.05). Foetal pulmonary artery vasoconstriction was induced by L-NAME with a decrease in internal diameter from 0.88 +/- 0.03 mm to 0.64 +/- 0.01 mm in control vs. L-NAME groups (p < 0.05), respectively. We conclude that perinatal NOS inhibition results in pulmonary artery vasoconstriction and a decreased tolerance to hyperoxia induced lung injury in newborn rats.

Nitric oxide inhibition causes intrauterine growth retardation and hind-limb disruptions in rats.

OBJECTIVE: Our purpose was to determine the effects of nitric oxide synthase inhibition on maternal and fetal health in the last third of pregnancy. STUDY DESIGN: Pregnant rats were treated from gestational day 13 to day 19 or 20 with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, which was administered in the drinking water ad libitum. Control animals received the inactive enantiomer NG-nitro-D-arginine methyl ester or no treatment. Maternal blood pressure, blood chemistry studies, and placenta and pup size were determined. A separate group of rats received nitroprusside sodium in conjunction with NG-nitro-L-arginine methyl ester. RESULTS: NG-nitro-L-arginine methyl ester caused a dose-dependent reduction in placenta and pup size. Amniotic fluid levels of cyclic guanosine monophosphate were significantly reduced at 0.1 mg/ml but not at higher doses. Hemorrhagic necrosis of fetal hind limbs occurred only with treatment with NG-nitro-L-arginine methyl ester and was prevented by coadministration of nitroprusside sodium. Maternal blood pressure and blood and urine chemistry studies were unaffected by NG-nitro-L-arginine methyl ester. CONCLUSION: Chronic reductions of nitric oxide production in the last third of pregnancy result in significant intrauterine growth retardation and hemorrhagic disruptions of hind limbs. Maternal complications were minimal and did not mimic preeclampsia.

Cardiopulmonary arrest secondary to lightning injury in a pregnant woman.

A young woman who was seven months pregnant was struck by lightning, resulting in cardiopulmonary arrest. Bystander CPR was begun at the scene. Vital signs were restored by the time the rescue squad arrived. The patient was comatose on arrival in the emergency department and fetal death was apparent. The patient's neurological status improved markedly, with a small residual motor deficit.