New Ventilator Strategies: High-Frequency Oscillatory Ventilation Combined with Volume Guarantee.

High-frequency oscillatory ventilation (HFOV) has been proposed as an alternative method of invasive ventilation in immature infants to prevent ventilator lung injury. To better control the size of the high-frequency tidal volume and to prevent large tidal volumes, a new strategy of controlling the tidal volume during HFOV (VThf) has been developed, HFOV-volume guarantee (VG). Data from preclinical, neonatal animal studies in normal and surfactant-depleted lungs have demonstrated the feasibility of this technique to directly control the VThf in the normal compliance and low compliance situations. Different I:E ratios also can modify the effect of CO2 washout during HFOV combined with VG in a different way as without the VG modality. Finally, clinical use of this technique in newborn infants has demonstrated the possibility of using very high frequency combined with constant very low VThf to decrease the risk of lung trauma related to the ventilator.

The newborn rat gastric emptying rate is volume and not developmentally dependent.

BACKGROUND: Gastric residuals are a common finding in enterally fed preterm neonates and traditionally thought to reflect immaturity-related delayed gastric emptying. Adult human data suggest that the meal volume regulate the gastric emptying rate, but early in life, this has not been adequately evaluated. The goal of this study was to study the rat postnatal changes in gastric emptying rate and the strain-induced effect on muscle contraction. We hypothesized that the stomach content volume and not developmental factors determines the newborn gastric emptying rate, via the Rho-kinase 2 (ROCK-2) pathway. METHODS: Gastric volume and emptying rate measurements were obtained by ultrasound at different postprandial times and the wall strain-dependent changes in muscle contraction were evaluated ex vivo. KEY RESULTS: The newborn rat gastric emptying rate was unrelated to postnatal age, maximal 30 min postprandial, and directly proportional to content volume. In vitro measurements showed that the agonist-induced gastric muscle contraction was directly proportional to the stomach wall strain. These changes were mediated via upregulation of ROCK-2 activity. CONCLUSIONS & INFERENCES: The newborn rat gastric emptying rate is not developmentally regulated, but dependent on the content volume via wall strain-induced ROCK-2 activation. Further clinical studies addressing the content volume effect on the rate of gastric emptying are warranted, to enhance feeding tolerance in preterm neonates.

Neonatal nasal intermittent positive pressure ventilation efficacy and lung pressure transmission.

OBJECTIVE: The objective of this study was to evaluate carbon dioxide (CO2) clearance, delivered pressures and tidal volume (VT) during neonatal nasal intermittent positive pressure ventilation (NIPPV) with two commonly used interfaces. STUDY DESIGN: A neonatal lung model, with either short binasal prongs (SBP) or a small caliber nasal cannula (RAM) interface, was tested over a range of clinically relevant settings. A fixed amount of CO2 was infused and the fraction remaining in the lung 100 s postinfusion was measured. Pressure transmission to the lung and VT was measured at the level of the trachea. RESULT: CO2 elimination was directly proportional to the inspiratory pressure during NIPPV. At peak pressures of 22 to 34 cm H2O, CO2 clearance was greater (P<0.001) with SBP as compared with RAM. Relative to the set ventilator parameters, a substantial pressure dampening effect was documented at the lung level, which was significantly lower with RAM when compared with SBP (2.8% (0.2) versus 11.9% (1.5), P<0.0001). CO2 elimination was dependent on VT and effective despite only a small fraction of physiological VT (maximum delivered VT%: SBP 15.5 (0.7) versus RAM 6.1 (1.4), P<0.0001). CONCLUSION: NIPPV promotes CO2 elimination even at low transmitted airway pressures, but less effective with RAM as compared with SBP. CO2 elimination despite small VT suggests that NIPPV may depend on a non-conventional gas-exchange mechanism.

Bringing back the old: time to reevaluate the high-frequency ventilation strategy.

OBJECTIVE: To examine the role of frequency in high-frequency ventilation (HFV) on carbon-dioxide (CO2) elimination and lung injury, independent of its effect on tidal volume. STUDY DESIGN: An anatomically representative lung model was attached to a mechanical ventilator capable of providing HFV with a constant volume. CO2 was infused directly into the lung, and a commercially available end-tidal CO2 detector was used to determine CO2 elimination. CO2 elimination and amplitude of pressure transmissions were evaluated using frequencies ranging from 5 to 15 Hz. The pressure-volume index (PVI) was described as the product of the volume and pressures delivered to the lung, a surrogate for lung injury. RESULT: The use of increasing frequencies directly correlated with improved CO2 clearance when keeping the tidal volume fixed, expressed as percent CO2 remaining in the lung at 25 s (66.5 (±1.1)%, 50.5 (±0.1)% and 37.8 (±0.3)% at 5, 10 and 15 Hz, respectively, P<0.05). With a fixed tidal volume, there was a decrease in pressure amplitudes transmitted to the lung with a decline in the PVI (53.9 (±2.7) mmHg ml(-1), 41.1 (±0.9) mmHg ml(-1) and 23.4 (±3.6) mmHg ml(-1), at 5, 10 and 15 Hz, respectively, P<0.05). CONCLUSION: Frequency has a direct relationship with CO2 elimination when tidal volume is fixed. Using low delivered tidal volumes and high frequencies may allow for improved ventilation efficacy, while minimizing lung injury.

Age-dependent endothelial nitric oxide synthase uncoupling in pulmonary arteries of endoglin heterozygous mice.

Endoglin is a TGF-beta superfamily receptor critical for endothelial cell function. Mutations in this gene are associated with hereditary hemorrhagic telangiectasia type I (HHT1), and clinical signs of disease are generally more evident later in life. We previously showed that systemic vessels of adult Eng heterozygous (Eng(+/-)) mice exhibit increased vasorelaxation due to uncoupling of endothelial nitric oxide synthase (eNOS). We postulated that these changes may develop with age and evaluated pulmonary arteries from newborn and adult Eng(+/-) mice for eNOS-dependent, acetylcholine (ACh-induced) vasorelaxation, compared with that of age-matched littermate controls. While ACh-induced vasorelaxation was similar in all newborn mice, it was significantly increased in the adult Eng(+/-) vs. control vessels. The vasodilatory responses were inhibited by l-NAME suggesting eNOS dependence. eNOS uncoupling was observed in lung tissues of adult, but not newborn, heterozygous mice and was associated with increased production of reactive O(2) species (ROS) in adult Eng(+/-) vs. control lungs. Interestingly, ROS generation was higher in adult than newborn mice and so were the levels of NADPH oxidase 4 and SOD 1, 2, 3 isoforms. However, enzyme protein levels and NADPH activity were normal in adult Eng(+/-) lungs indicating that the developmental maturation of ROS generation and scavenging cannot account for the increased vasodilatation observed in adult Eng(+/-) mice. Our data suggest that eNOS-dependent H(2)O(2) generation in Eng(+/-) lungs accounts for the heightened pulmonary vasorelaxation. To the extent that these mice mimic human HHT1, age-associated pulmonary vascular eNOS uncoupling may explain the late childhood and adult onset of clinical lung manifestations.

Rat pulmonary arterial smooth muscle myosin light chain kinase and phosphatase activities decrease with age.

We and others have shown that the fetal pulmonary arterial smooth muscle potential for contraction and relaxation is significantly reduced compared with the adult. Whether these developmental changes relate to age differences in the expression and/or activity of key enzymes regulating the smooth muscle mechanical properties has not been previously evaluated. Therefore, we studied the catalytic activities and expression of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) catalytic (PP1cdelta) and regulatory (MYPT) subunits in late fetal, early newborn, and adult rat intrapulmonary arterial tissues. In keeping with the greater force development and relaxation of adult pulmonary artery, Western blot analysis showed that the MLCK, MYPT, and PP1cdelta contents increased significantly with age and were highest in the adult rat. In contrast, their specific activities (activity/enzyme content) were significantly higher in the fetal compared with the adult tissue. The fetal and newborn pulmonary arterial muscle relaxant response to the Rho-kinase inhibitor Y-27632 was greater than the adult tissue. In addition to the 130-kDa isoform of MLCK, we documented the presence of minor higher-molecular-weight embryonic isoforms in the fetus and newborn. During fetal life, the lung pulmonary arterial MLCK- and MLCP-specific activities are highest and appear to be related to Rho-kinase activation during lung morphogenesis.

Bronchial epithelium-associated pulmonary arterial muscle relaxation in the rat is absent in the fetus and suppressed by postnatal hypoxia.

We recently reported the existence of a bronchial epithelium-derived relaxing factor (BrEpRF) capable of reducing pulmonary arterial smooth muscle force generation in the newborn rat. We reasoned in this study that BrEpRF has physiological significance in the control of pulmonary vascular tone. We hypothesized that the release and/or activity of this factor can be stimulated and is suppressed prenatally or under hypoxic conditions postnatally. Therefore, we evaluated the pathways stimulated by the BrEpRF in fetal and newborn rat intrapulmonary arteries mounted with their adjacent bronchi in a wire myograph under both normoxic and hypoxic conditions. Under normoxic conditions, BrEpRF release/activation was observed in newborn vessels following methacholine stimulation of M(2) muscarinic receptors, which was mediated via a nitric oxide (NO)-dependent mechanism involving the phosphatidylinositol 3-kinase pathway. Hypoxia suppressed the BrEpRF-dependent modulation of basal and methacholine-induced pulmonary arterial muscle tone in newborn vessels without altering endothelium-dependent or -independent NO-mediated relaxation. In fetal pulmonary arteries studied under normoxic conditions, BrEpRF neither was active under basal conditions nor could it be stimulated with methacholine. We conclude that release/activation of the BrEpRF occurs by an oxygen-dependent mechanism in the newborn and is suppressed during late fetal life. These results suggest that the BrEpRF may be involved in postnatal adaptation of the pulmonary circulation and that its suppression may contribute to hypoxic pulmonary vasoconstriction.

A bronchial epithelium-derived factor reduces pulmonary vascular tone in the newborn rat.

The factors accounting for the maintenance of a low pulmonary vascular resistance postnatally are not completely understood. The aim of this study was to test the hypothesis that bronchial epithelium produces a factor capable of relaxing adjacent pulmonary arterial smooth muscle. We studied fourth-generation intralobar pulmonary arteries and bronchi of 4- to 8-day-old rats. Arteries were mounted on a wire myograph, alone or with the adjacent bronchus. The presence of the attached bronchus significantly reduced pulmonary artery force generation induced by the thromboxane analog (U-46619) or KCl whether the endothelium was present or absent (P < 0.01). The converse was not true in that bronchial force generation was not affected when studied with the adjacent pulmonary artery. Mechanical removal of the bronchial epithelium or addition of the nitric oxide (NO) synthase (NOS) nonspecific (N(G)-monomethyl-l-arginine) or the specific neuronal NOS (7-nitroindazole) inhibitors increased arterial force generation to levels comparable to the isolated artery preparation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, significantly decreased (P < 0.01) NO release of pulmonary arteries only when the adjacent bronchus was present. We conclude that bronchial epithelium in the newborn rat produces a factor capable of lowering pulmonary vascular muscle tone. This relaxant effect can be suppressed by NOS and phosphatidylinositol 3-kinase kinase inhibition, suggesting an action via NOS phosphorylation and NO release. We speculate that such a mechanism may be operative in vivo and plays an important role in control of pulmonary vascular resistance in the early postnatal period.

Chronic O2 exposure in the newborn rat results in decreased pulmonary arterial nitric oxide release and altered smooth muscle response to isoprostane.

Chronic oxygen exposure in the newborn rat results in lung isoprostane formation, which may contribute to the pulmonary hypertension evident in this animal model. The purpose of this study was to investigate the pulmonary arterial smooth muscle responses to 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2a)) in newborn rats exposed to 60% O2 for 14 days. Because, in the adult rat, 8-iso-PGF(2alpha) may have a relaxant effect, mediated by nitric oxide (NO), we also sought to evaluate the pulmonary arterial NO synthase (NOS) protein content and NO release in the newborn exposed to chronic hyperoxia. Compared with air-exposed control animals, 8-iso-PGF(2a) induced a significantly greater force (P < 0.01) and reduced (P < 0.01) relaxation of precontracted pulmonary arteries in the 60% O2-treated animals. These changes were reproduced in control pulmonary arteries by NOS blockade by using NG-nitro-L-arginine methyl ester. Pulmonary arterial endothelial NOS was unaltered, but the inducible NOS protein content was significantly decreased (P < 0.01) in the experimental group. Pulmonary (P < 0.05) and aortic (P < 0.01) tissue ex vivo NO accumulation was significantly reduced in the 60% O2-treated animals. We speculate that impaired pulmonary vascular tissue NO metabolism after chronic O2 exposure potentiates 8-iso-PGF(2alpha)-induced vasoconstriction in the newborn rat, thus contributing to pulmonary hypertension.

Effect of 8-isoprostaglandin F2alpha on the newborn rat pulmonary arterial muscle and endothelium.

8-Isoprostaglandin F2alpha (8-iso-PGF2alpha) is a bioactive lipid peroxidation product that is a vasoconstrictor at high concentrations. Paradoxically, at lower, and possibly physiological, concentrations, it is a pulmonary vascular muscle's relaxant. Its effects on newborn pulmonary vasculature are unknown. We hypothesized that the pulmonary arterial 8-iso-PGF2alpha responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF2alpha effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 microm) mounted on a myograph. Force after 8-iso-PGF2alpha stimulation was greatest in the adult (P < 0.01). In newborns, force was significantly increased by the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (P < 0.01) and was suppressed by blockade of the thromboxane (Tx) A2 receptor. Whereas 8-iso-PGF2alpha induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA2 mimetic (U-46619; 1 microM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF2alpha-induced contraction was abolished by endothelium removal and l-NAME and was attenuated by the cyclooxygenase inhibitor ibuprofen. In the presence of a TxA2/prostaglandin H2 receptor blocker, 8-iso-PGF2alpha induced NO-mediated relaxation, the magnitude of which was greater in the newborn, compared with the adult (P < 0.01). When exposed to 8-iso-PGF2alpha in vitro, only the newborn lung secreted TxB2. We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF2alpha induces contraction of the pulmonary arteries in the early postnatal period, which is likely to be mediated by endothelium-derived TxA2. This phenomenon may contribute to the maintenance of a higher pulmonary vascular resistance in the early postnatal period.

Chronic O2 exposure enhances vascular and airway smooth muscle contraction in the newborn but not adult rat.

Neonatal rats exposed to 60% O(2) for 14 days develop lung changes compatible with human bronchopulmonary dysplasia and pulmonary hypertension. Our aim was to evaluate and compare the newborn and adult rat pulmonary vascular and airway smooth muscle force generation and relaxation potential after exposure to 60% O(2) for 14 days. Vascular and airway intrapulmonary rings 100 microm in diameter were mounted on a myograph and bathed in Krebs-Henseleit solution bubbled with air- 6% CO(2) at 37 degrees C. Significant age-dependent changes in intrapulmonary arteries and their neighboring airway muscle properties were observed. Whereas hyperoxia enhanced force in neonatal vascular and airway muscle, the opposite was seen in adult samples. No changes in endothelium-dependent vascular relaxation were observed at either age, but the dose response to an endothelium-independent NO donor was altered. In the newborn experimental animals, the relaxation was reduced, whereas, in their adult counterparts, it was enhanced. After O(2) exposure, the bronchial muscle relaxation response to epithelium-dependent and -independent stimulation was not altered in either age group, whereas the epithelium-dependent response was decreased only in the adult. The antioxidant Trolox, or an endothelin-A and -B receptor antagonist, reversed the vascular and airway muscle's hyperoxia-induced changes. We conclude that chronic O(2) exposure in the newborn rat results in enhanced lung vascular and airway muscle contraction potential via a mechanism involving reactive oxygen species and the endothelin pathway. The present findings also suggest that the newborn is more susceptible to airway hyperresponsiveness after chronic O(2) exposure.

Age-dependent changes in the regulation of cyclooxygenases in the gastrointestinal tract after gram-negative endotoxemia.

BACKGROUND: Cyclooxygenases (COXs) modulate prostaglandin synthesis in the gastrointestinal tract. Prostaglandins have been shown to have a cytoprotective effect on bowel mucosa in adults, but no similar data are available in neonates. Thus, the purpose of the current study was to evaluate age-dependent changes in gastrointestinal tract COX regulation after Escherichia coli lipopolysaccharide exposure in rats. METHODS: Stomach, small bowel, and large bowel COX-1 and COX-2 mRNA levels (reverse transcription polymerase chain reaction technique) and protein content (Western blot) were obtained from neonates (younger than 3 days old) and adult rats 18 hours after exposure to E. coli O111:B4 lipopolysaccharide toxin. Untreated animals served as controls. RESULTS: Stomach, small bowel, and large bowel tissue COX-1 mRNA levels in the newborn were significantly lower (P < 0.01) than in the adult. No age-dependent differences were found for COX-2 mRNA levels. After lipopolysaccharide exposure, no significant changes in COX-1 levels were seen at either age, whereas COX-2 mRNA levels were increased only in the stomach for both ages. Western blot analysis of small bowel tissue for COX-1 and COX-2 showed no lipopolysaccharide-induced changes in protein content, but the COX-1 content was significantly lower in the newborn (P < 0.01). CONCLUSIONS: In the rat, COX expression in the gastrointestinal tract is regulated in an age-dependent fashion. Lower COX-1 expression and a lack of observable increase in COX-2 mRNA levels in the newborn small bowel after endotoxemia may render the bowel more susceptible to bowel injury early in life.

Progressive lung and cardiac changes associated with pulmonary hypertension in the fetal rat.

To determine the natural history of lung vascular remodeling and cardiac changes in the rat model of persistent pulmonary hypertension syndrome (PPHN) of the newborn, we studied fetal rats subjected to maternal indomethacin administration initiated on day 19 of gestation and continued for 2, 3, or 4 days. Animals receiving a similar volume of water or alcohol served as controls. Significant pulmonary hypertension was noted in the experimental group, as evidenced by a significantly increased right to left ventricular wall ratio to 1.6 +/- 0.1 in the 4-day treatment group, as compared with 1.2 +/- 0.4 in the control group (P < 0.01). The smooth muscle area for <25 microm external diameter arterial vessels was significantly increased (12.7 +/- 0.6 vs. 10.0 +/- 0.6 microm; P < 0.01) and the adventitial area of all diameters vessels was significantly greater (P < 0.01) following 3 days of indomethacin treatment, as compared with water controls. Associated with these changes, the 4-day treatment group's lung/body weight ratio was 0.021 +/- 0.001, and was significantly less (P < 0.01) than for the control group (0.035 +/- 0.001). This reduction in lung weight was not associated with changes in lung protein content or wet/dry weight ratio, indicating that pulmonary hypertension in the fetal rat induced lung hypoplasia. In conclusion, closure of the ductus arteriosus in the fetal rat results in early-onset right ventricular hypertrophy, followed by pulmonary vascular remodeling and lung hypoplasia. We speculate that lung growth in late gestation is adversely affected by pulmonary hypertension.

Continuous infusion of glucagon induces severe hyponatremia and thrombocytopenia in a premature neonate.

We report on a 35-week gestation infant who developed severe hyponatremia and thrombocytopenia after continuous infusion of glucagon for the treatment of intractable hypoglycemia. Given these serious side effects,glucagon infusion should be avoided in the treatment of premature infants.hypoglycemia, glucose, small for gestational age. Hypoglycemia is commonly seen in premature infants, and the provision of a standard glucose intake is often not sufficient to maintain euglycemia. For these infants, an increase in glucose infusion to provide 4 to 8 mg/kg/min is initially recommended.1 Should this approach fail, pharmacologic agents such as corticosteroids or diazoxide are indicated.1 When the serum glucose in premature or small for gestational age infants cannot be adequately maintained, a glucagon infusion is now suggested as the best treatment approach.2,3 We report the use of glucagon infusion for the treatment of severe hypoglycemia in a premature infant. A severe hyponatremia associated with transient convulsions and thrombocytopenia was observed in the neonate after treatment. Discontinuation of the glucagon infusion resulted in prompt resolution of these abnormalities.

[Critical analysis of the use of corticosteroids in the neonatal period] / Análise crítica do uso de esteróides no período neonatal.

OBJECTIVE: To review the use of corticosteroids in the treatment of newborns with chronic lung disease, adrenal insufficiency and upper airway edema. SOURCES: Review of the available medical literature on the use of corticosteroids in newborns. SUMMARY OF THE FINDINGS: Although there is evidence of short-term clinical improvement of chronic lung disease with the administration of dexamethasone, the available literature did not show significant reduction in neonatal morbidity and mortality associated with this condition. CONCLUSIONS: The use of corticosteroids must be carefully analyzed and restricted to the treatment of severe cases, since these drugs may produce irreversible effects on the nervous system and neurological development of newborns.

Effect of budesonide and salbutamol on surfactant properties.

The objective of this study was to evaluate the in vitro effect of budesonide and salbutamol on the surfactant biophysical properties. The surface-tension properties of two bovine lipid extracts [bovine lipid extract surfactant (BLES) and Survanta] and a rat lung lavage natural surfactant were evaluated in vitro by the captive bubble surfactometer. Measurements were obtained before and after the addition of a low and high concentration of budesonide and salbutamol. Whereas salbutamol had no significant effect, budesonide markedly reduced the surface-tension-lowering properties of all surfactant preparations. Surfactant adsorption (decrease in surface tension vs. time) was significantly reduced (P < 0.01) at a high budesonide concentration with BLES, both concentrations with Survanta, and a low concentration with natural surfactant. At both concentrations, budesonide reduced (P < 0.01) Survanta film stability (minimal surface vs. time at minimum bubble volume), whereas no changes were seen with BLES. The minimal surface tension obtained for all surfactant preparations was significantly higher (P < 0.01), and the percentage of film area compression required to reach minimum surface tension was significantly lower after the addition of budesonide. In conclusion, budesonide, at concentrations used therapeutically, adversely affects the surface-tension-lowering properties of surfactant. We speculate that it may have the same adverse effect on the human surfactant.

Pulmonary and systemic vascular tissue collagen, growth factor, and cytokine gene expression in the rabbit.

During development, the vascular wall composition of the pulmonary and systemic capacitance vessels and their intravascular pressure changes. Little is known, however, about the factors controlling vascular collagen gene expression in both circulations during growth and development. The purpose of this study was to compare the developmental changes in collagen, major growth factors, and cytokines gene expression, in order to ascertain whether a circulation specific pattern is present in the rabbit. Fetal, neonatal, and adult rabbit extrapulmonary and aortic tissues were obtained and the mRNA levels for collagen I and III, as well as major growth factors and cytokines, were measured by a semi-quantitative RT-PCR technique. Collagen I, but not collagen III, expression was developmentally regulated in pulmonary vascular and aorta tissues. Collagen I expression was greatest during the fetal and neonatal period (P < 0.01) and higher in the aorta as compared with the pulmonary artery at these ages (P < 0.05). Significant developmental changes in growth factor mRNA levels were observed for TGF-beta, IGF-2, and bFGF (P < 0.01). IGF-2 mRNA levels significantly declined in both arteries from neonatal to adult, but bFGF increased only in the pulmonary artery during this transition. With regards to inducible enzymes, COX-2 mRNA levels changed developmentally, whereas iNOS mRNA levels were similar for both vessels at all ages. When comparing the two vessels, COX-2 transcripts were relatively more abundant in the adult pulmonary artery tissue and fetal aorta, with similar levels in the newborn. We conclude that circulation specific developmental regulation of collagen gene expression is present in the rabbit in a pattern that is unrelated to the intravascular pressure.

Effects of in vitro fertilization on low birth weight, preterm delivery, and multiple birth.

PURPOSE: To quantify the contribution of in vitro fertilization (IVF) on changes in the rates of low birth weight (LBW), preterm delivery, very low birth weight, and multiple births during the past 3 years. METHODS: Data on IVF pregnancies from 1994 to 1996 within Alberta were reviewed. Population data were obtained from the Provincial notice of a live or stillbirth. RESULTS: The IVF component of increased LBW rate in the province was 17.8% for infants <2500 g and 43.5% for those born <1500 g. IVF accounted for 10.5% of the provincial rate increase in deliveries <37 weeks' gestation and 66.2% of those <30 weeks' gestation. IVF accounted for 21.4% of the twins and all of the sets of triplets in the province. CONCLUSION: During a 3-year period IVF has affected the incidence of LBW, preterm delivery, and multiple birth. IVF is a substantial contributor to changes in very low birth weight and delivery before 30 weeks, which is partly related to multiple births.

Breast milk supplementation for preterm infants: parental preferences and postdischarge lactation duration.

Breast milk supplementation is frequently used to improve preterm infant growth and to achieve satisfactory intakes of minerals and vitamins. In the North American market there are commercial preparations: two powders and a liquid. The nutritional data available suggest these products are similar and their utilization is based on healthcare team choice. Parental perception about supplementation has not been previously evaluated although parental attitudes are known to impact on lactation success. The objectives of this paper are to determine parental preference and breastfeeding duration for very-low-birth-weight infants given commercial breast milk enrichment products. The study design is a randomized clinical trial with parental interviews. Sixty-three families with 71 infants were enrolled. Parents expressed their preference for the addition of a powder over a liquid preparation (p<0.01). Those mothers whose infants received the liquid enrichment had a shorter lactation relative to their goal, compared with the mothers of the infants who received the powder (p = 0.017). Parents prefer a powder product for breast milk supplementation and this choice positively impacts on the duration of breastfeeding for very-low-birth-weight infants.

Urethane suppresses rat lung inducible cyclooxygenase and nitric oxide synthase mRNA levels.

OBJECTIVE AND DESIGN: The purpose of the present study was to evaluate the effect of urethane, pentobarbital sodium and ketamine-xylazine anesthesia upon constitutive and inducible cyclooxygenase (COX-1; COX-2) and nitric oxide synthase (eNOS; iNOS) mRNA levels in the lung. METHODS: mRNA levels were determined by the semiquantitative RT-PCR technique. TREATMENT: Urethane (1.1 g/kg ip), Pentobarbital Sodium (40 mg/kg ip), and ketamine (85 mg/kg) - xylazine (15 mg/kg, im). Non-anesthetized animals served as controls. MATERIAL: Sprague-Dawley rat lungs RESULTS: Urethane significantly decreased COX-1 and COX-2 mRNA levels to 30% of control values. This agent had no effect upon eNOS, but completely suppressed iNOS mRNA levels. Pentobarbital sodium and ketamine had no effect on the mRNA levels for COX-1 and COX-2 the lung. CONCLUSIONS: Urethane has a suppressive effect on COX and iNOS RNA message in the lung and for this reason it should be avoided as an anesthetic when lung inflammatory processes are experimentally evaluated in the rat.