Circadian periodicity of bone marrow mitotic activity and reticulocyte counts in rats and mice.

Mitotic proliferation in the bone marrow of female rats and mice kept under standardized coniditions with light from 6:00 a.m. to 6:00 p.m. exhibited a significant circadian periodicity with the greatest activity occurring from 6:00 a.m. to 12:00 noon. The reticulocyte levels in peripheral blood were highest at 8:00 a.m.

The influence of amino-acid supplementation, gestational age and time on thyroxine levels in premature neonates.

OBJECTIVE: Newborn screening laboratories vary in the values that are used to define congenital hypothyroidism. Defining congenital hypothyroidism is particularly complex in premature neonates because prematurely born infants often have a low free thyroxine value and low or normal TSH value, termed as transient hypothyroxinemia of prematurity. In a multicenter (n=11 sites) trial, we randomly allocated premature neonates with a gestational age of 23 to 29 and 6/7 weeks to one of two parenteral nutrition approaches. The primary objective of our trial was to measure the effect of two distinct strategies of parenteral nutrition on neonatal growth and blood amino acids. A protocol defined secondary aim of our clinical trial was the evaluation of the influence of gestational age, time and the degree of amino-acid supplementation on total thyroxine levels. We hypothesized that an increase of amino-acid supplementation would be associated with the normalization of serum amino acids and that this would improve thyroxine synthesis. STUDY DESIGN: Premature neonates (23 to 29 and 6/7 weeks) were randomly allocated to one of two approaches to intravenous amino-acid administration. In one group, amino-acid supplementation started at 1.0 g kg(-1) per day and advanced by 0.5 g kg(-1) per day to a maximum of 2.5 g kg(-1) per day (2.5 group). The other group received amino acids at 1.5 g kg(-1) per day and advanced by 1.0 g kg(-1) per day to a maximum of 3.5 g kg(-1) per day (3.5 group). Filter paper blood spots were obtained on the day of randomization, and on days 7 and 28 of age to monitor laboratory values. RESULT: Enrollment included 122 neonates, 64 in the 3.5 group and 58 in the 2.5 group. There were no differences in demographics or baseline characteristics between the two treatment groups. There were no significant differences in thyroid levels at baseline, on days 7 and 28 between the two treatment groups. Growth was similar in both groups. It was noted that thyroxine levels changed over time and that the changes with time were greatest in the most preterm neonates. CONCLUSION: The degree of amino-acid supplementation does not influence thyroxine levels and both time from birth and gestational age do influence thyroxine levels.

Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant.

OBJECTIVE: The primary aim of this study was to determine if an association exists between amino-acid levels and development of cholestasis. The secondary aim of our amino-acid dose comparison trial was to identify factors associated with the development of prolonged cholestatic jaundice. STUDY DESIGN: We compared demographic characteristics and amino-acid levels in neonates who developed cholestasis with those who did not. Parenteral-associated cholestatic liver disease was defined as a direct serum bilirubin above 5 mg per 100 ml any time during the first 28 days after birth in neonates with no history of biliary atresia or viral hepatitis. We obtained filter paper blood spots for amino acid and acylcarnitine measurements on the day of randomization and days 7 and 28 of age to identify a profile of values that could be used to identify neonates with evidence of abnormal liver function. RESULT: We enrolled 122 neonates in our study; 13 (10.7%) developed cholestasis. Neonates who developed cholestasis were more immature, had lower birth weight, were exposed to parenteral nutrition for a longer period, had a higher cumulative dose of amino acids, were less often on enteral nutrition by day 7 of age, more often had a patent ductus arteriosus and severe intraventricular hemorrhage and were more commonly treated with steroids by 28 days of age. Amino acid and acylcarnitine values were not different for the two groups on the day of randomization. On day 7 (parenteral phase of nutrition), blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine were higher, and serine, glutamate and thyroxine levels were lower in the neonates who developed cholestasis than in who did not. CONCLUSION: Cholestasis remains an important complication of parenteral nutrition, and several clinical and biochemical factors may be helpful in identifying high-risk patients.

Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

OBJECTIVE: Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS. STUDY DESIGN: This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded. RESULTS: Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001). CONCLUSION: Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.

Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures.

OBJECTIVE: The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis. STUDY DESIGN: We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram stain for yeast. We calculated two-tailed P-values using non-parametric testing, Mann-Whitney, Kruskal-Wallis or Fisher's exact tests where appropriate. RESULTS: Twenty infants had culture-positive Candida meningitis. Normal CSF parameters were found in 43% (3/7) of the infants with Candida meningitis and only 37% (7/19) of them had positive blood cultures for Candida. CONCLUSION: Normal CSF parameters do not exclude the diagnosis of neonatal Candida meningitis. The majority of infants in this cohort with Candida meningitis did not have evidence of candidemia at the time of diagnosis.

Impact of l-carnitine supplementation on metabolic profiles in premature infants.

OBJECTIVE: To describe the influence that of l-carnitine supplementation on acylcarnitine (AC) profiles and hospital outcomes in premature infants. STUDY DESIGN: This study is a secondary analysis of previously reported work. Metabolic profiles were obtained using standard newborn techniques on infants born between 23 and 31 completed weeks of gestation. The profiles were drawn within the first 24 h after birth and on approximately days 7, 28 and 42 of life, or at the time of discharge. A single, central, contract laboratory analyzed and managed the samples. RESULTS: We studied 995 patients; none was subsequently diagnosed with an inborn error of metabolism. l-Carnitine was added to parenteral nutrition in 390 (39%) study subjects; 592 (60%) did not receive supplementation. Non-supplemented infants were more likely to develop low levels of free carnitine (FC; <7 µm) on day 28; (41% vs 5%, P<0.01); and FC values were lower on day 7. Despite higher levels of FC and fewer patients with significant carnitine deficiencies, we found no evidence that l-carnitine supplementation was associated with improved short-term hospital outcomes. CONCLUSION: l-Carnitine supplementation is common in prematurely born neonates and is associated with higher carnitine levels, but is not associated with improved short-term hospital outcomes.

Association of in utero magnesium exposure and spontaneous intestinal perforations in extremely low birth weight infants.

OBJECTIVE: The objective of this study is to determine whether antenatal exposure to magnesium is associated with spontaneous intestinal perforation (SIP) in extremely low birth weight (ELBW) infants (⩽1000 g). STUDY DESIGN: We identified all ELBW infants admitted to 1 of 323 neonatal intensive care units from 2007 to 2013. We used multivariable conditional logistic regression to compare outcomes in the first 21 days after birth between infants exposed and unexposed to magnesium in utero. RESULTS: Of the 28 035 infants, 11 789 (42%) were exposed to antenatal magnesium (AM). There was no difference in the risk of SIP, odds ratio=1.08 (95% confidence interval; 0.91 to 1.29), between infants exposed and unexposed to AM. Mortality in the first 21 days after birth was lower in the magnesium-exposed infants, odds ratio=0.76 (0.70 to 0.83). CONCLUSION: AM exposure in ELBW infants was not associated with increased risk of SIP.

Changing antiepileptic drug use for seizures in US neonatal intensive care units from 2005 to 2014.

OBJECTIVE: Neonatal seizures are a common problem in the neonatal intensive care unit and are frequently treated with antiepileptic drugs. Limited data exist on current or changing antiepileptic drug use for seizures in the neonatal intensive care unit.We sought to describe trends of antiepileptic drug exposure in a large volume of US neonatal intensive care unit from 2005 to 2014 and we hypothesized increasing levetiracetam exposure over the 10-year study period. STUDY DESIGN: Retrospective cohort study of infants from the Pediatrix Medical Group Clinical Data Warehouse, a large, multicenter, deidentified data set. Data were analyzed for trends in 2-year time periods. Our cohort included infants with a diagnosis of seizures who received an antiepileptic drug that were discharged from the neonatal intensive care unit from 1 January 2005 to 31 December 2014. RESULTS: Among 778 395 infants from 341 facilities, we identified 9134 infants with a seizure diagnosis who received an antiepileptic drug. Phenobarbital was used in 98% of the cohort. From 2005-2006 to 2013-2014 phenobarbital exposure declined from 99 to 96% (P<0.001), phenytoin exposure decreased from 15 to 11% (P<0.001) and levetiracetam exposure increased 10-fold from 1.4 to 14% (P<0.001). Overall, <1% of infants were exposed to carbamazepine, lidocaine or topiramate. CONCLUSIONS: Infants with seizures were overwhelmingly exposed to phenobarbital, despite a significant increase in levetiracetam exposure. The use of phenytoin declined and has been surpassed by levetiracetam as the second most widely used antiepileptic in the neonatal intensive care unit. These changes in antiepileptic drug usage patterns have occurred in the absence of novel efficacy data in neonates.

Risk factors for group B streptococcal disease in neonates of mothers with negative antenatal testing.

OBJECTIVE: The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening. STUDY DESIGN: We performed a retrospective cohort study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS. RESULTS: EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)). CONCLUSION: Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.

The epidemiology, prevalence and hospital outcomes of infants with gastroschisis.

OBJECTIVE: The purpose of this study is to evaluate recent trends in prevalence of gastroschisis among infants admitted for neonatal intensive care in the United States. STUDY DESIGN: Retrospective review of a de-identified patient data. The current study extends our observations through the end of 2007 to 2015. RESULTS: During the study period (1 January 1997 to 12 December 2015), there were 1 158 755 total discharges; 6023 (5.2/1000) had gastroschisis and 1885 (1.6/1000) had an omphalocele. Between 1997 and 2008, the reported rate of gastroschisis increased from 2.9 to 6.4/1000 discharges. From 2008 to 2011, the values have slowly decreased from 6.4 to 4.7/1000 discharges and since 2011 have been stable. The largest drop in the prevalence was in mothers who were <20 years old. In contrast, the reported rate of omphalocele was stable at 1 to 2/1000 discharges. CONCLUSION: The prevalence of gastroschisis increased from 1997 to 2008, and then declined thereafter.

Sildenafil and retinopathy of prematurity risk in very low birth weight infants.

OBJECTIVE: To examine the effect of sildenafil therapy on development of severe retinopathy of prematurity (ROP) requiring surgical intervention in premature infants. STUDY DESIGN: We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care units from 2003 to 2012 and who received an ophthalmologic exam. We matched each infant exposed to sildenafil before first eye exam to three nonexposed infants using propensity scoring to control for differences in baseline infant characteristics. We evaluated the association between sildenafil exposure and development of severe ROP using conditional logistic regression. RESULT: Of the 57 815 infants meeting inclusion criteria, 88 were exposed to sildenafil. We matched 81/88 (92%) sildenafil-exposed with 243 nonexposed infants. There was no difference in the proportion of infants who developed severe ROP in the sildenafil-exposed vs nonexposed groups (17/81 (21%) vs 38/243 (16%), P=0.27). On adjusted analysis, there was no difference in severe ROP in the sildenafil-exposed vs nonexposed infants (odds ratio=1.46, 95% confidence interval=0.76 to 2.82, P=0.26). CONCLUSION: We did not observe an association between risk of severe ROP and sildenafil exposure before first eye exam in this cohort of premature infants.

Venovenous extracorporeal membrane oxygenation affects renal function.

OBJECTIVE: We evaluated the effect of venovenous extracorporeal membrane oxygenation (ECMO) on renal function and fluid balance in neonates with severe respiratory failure. DESIGN: We retrospectively reviewed the charts of 30 consecutive patients who met criteria for treatment with ECMO. Twelve were managed without ECMO (comparison group) and 18 were treated with venovenous ECMO (treatment group). SETTING: The study was conducted in a single level III neonatal intensive care unit in a regional children's hospital accepting medical and surgical neonatal transfers. Our hospital does not have an inborn service. PATIENTS: Neonates were included if their gestational age was more than 34 weeks, they weighed more than 2 kg, and their respiratory failure was severe enough to warrant consideration of ECMO as a mode of support. All the neonates in this study were treated with high-frequency ventilation before being considered for ECMO; none were treated with nitric oxide. Criteria used to determine whether a neonate was a candidate for ECMO included: (1) alveolar-arterial oxygen difference greater than 60 kPa (610 torr) for 8 hours; (2) alveolar-arterial oxygen difference greater than 59 kPa (605 torr) and a peak airway pressure greater than 3.7 kPa (38 cm H2O) for 4 hours; (3) oxygenation index greater than 40 on three of five postductal blood gases obtained at least 30 minutes apart and unstable patient condition; or (4) refractory, severe respiratory failure with sudden decompensation (partial pressure of arterial oxygen 3.4 kPa or lower, 35 torr) despite maximal medical management for 2 hours. We did not include patients with congenital diaphragmatic hernia. MAIN RESULTS: There were no differences between the groups in gestational age, birth weight, age at admission, gender, or diagnoses. Over the course of the 108 hours reviewed for each case, neonates treated with ECMO had higher positive fluid balance (P < .001), lower urine flow rates (P < .01), and higher blood urea nitrogen (P < .01) and creatinine (P < .01) levels than neonates managed without ECMO. There were no differences in mean blood pressure, protein intake, serum albumin, or use of diuretic therapy that might explain the differences between the groups. CONCLUSION: We conclude that venovenous ECMO is associated with transient impairment in renal function and marked fluid retention.

Congenital juvenile chronic myelogenous leukemia: case report and review.

The case of a patient with ecchymosis, hepatomegaly, leukocytosis, thrombocytopenia, and anemia at birth is presented. Throughout his course, thrombocytopenia, anemia, and leukocytosis without a marked increase in the number of blast forms in either peripheral blood or bone marrow persisted until the patient developed a blast crisis shortly before his death at age 4 months. This patient is the youngest reported to have the juvenile form of chronic myelogenous leukemia and the first that in the present era can be considered congenital in origin.

Predictors of failure of high-frequency oscillatory ventilation in term infants with severe respiratory failure.

OBJECTIVE: To identify clinical factors in term neonates with severe respiratory failure that predict which neonates are unlikely to respond to high-frequency oscillatory ventilation (HFOV). DESIGN: This was a retrospective review of patient charts and medical records. PATIENTS: We studied 190 newborns treated with HFOV between July 1985 and December 1992. All patients were at least 35 weeks' estimated gestational age and had severe respiratory failure, defined as arterial to alveolar oxygen ratio (a/A ratio) of less than 0.2 or the need for peak inspiratory pressure greater than 35 cm H2O on conventional ventilation. RESULTS: Of the 190 patients, 111 (58%) responded to HFOV (HFOV responders), and 79 (42%) were placed on extracorporeal membrane oxygenation (ECMO) after HFOV failed to improve gas exchange (nonresponders). The two groups were similar in gender and birth weight. Factors associated with failure of HFOV to produce a sustained improvement in gas exchange were a diagnosis of congenital diaphragmatic hernia and more severe respiratory compromise as assessed by admission blood gas. Stepwise logistic regression analysis showed that a diagnosis of congenital diaphragmatic hernia/lung hypoplasia (CDH/LH) and the a/A ratio at initiation of and after 6 hours of HFOV were the only significant independent predictors of the need for ECMO. Among all the patients, the presence of CDH/LH or an initial a/A ratio of 0.05 or lower yielded a sensitivity of 74% and specificity of 77% in correctly identifying neonates in whom HFOV failed to produce a sustained improvement in oxygenation. When neonates with CDH/LH were excluded from analysis, the most significant predictor of failure of HFOV was the a/A ratio after 6 hours of HFOV. In neonates without CHD/LH, a 6-hour a/A ratio of 0.08 or lower discriminated responders from nonresponders (ie, treatment with ECMO) with a sensitivity of 77% and specificity of 92%. CONCLUSIONS: In our patients, the presence of CDH/LH, severe respiratory failure (a/A ratio 0.05 or lower) at initiation of HFOV, and lack of improvement in oxygenation (a/A ratio 0.08 or lower after 6 hours of HFOV) were associated with failure of HFOV and treatment with ECMO. This information should help other centers to identify neonates who are at the greatest risk for requiring ECMO support and thus allow prompt transfer to an ECMO center.

Effect of maternal race on outcome of preterm infants in the military.

Previous studies suggest that low birth weight black infants have less morbidity and birth-weight-specific mortality during the perinatal period than low birth weight white infants. We studied the effect of maternal race on outcome in preterm infants born at a military hospital that offers free access to obstetric and neonatal care. Between January 1, 1986, and December 31, 1991, data were prospectively collected on all 667 infants delivered at Wilford Hall USAF Medical Center with an estimated gestational age of less than 35 weeks. Three hundred ninety-two white infants and 165 black infants were included in the data analysis. The mean (+/- SD) birth weight was 1701 +/- 65 g for white infants and 1462 +/- 66 g for black infants. The mean estimated gestational age was 31.0 +/- 3.2 weeks for white infants and 29.9 +/- 3.8 weeks for black infants. Preeclampsia was more frequent in black mothers than in white mothers for the entire study population (21% vs 14%), but the birth weight differential between races remained after correction for preeclampsia. There were no significant differences between races in stillbirths, gender, maternal age, maternal transfer status, number of prenatal visits, or percentages of mothers with small-for-gestational-age infants, multiple-gestation infants, prolonged rupture of membranes, or initial prenatal visit during the first trimester. Intraventricular hemorrhage was more frequent in white infants at 27 through 29 weeks estimated gestational age (50% vs 13%). There were no significant differences between the two groups in survival or in the occurrence of severe intraventricular hemorrhage or bronchopulmonary dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective randomized comparison of high-frequency oscillatory and conventional ventilation in respiratory distress syndrome.

A prospective randomized trial with a crossover design was conducted to compare the efficacy and safety of two distinct strategies of high-frequency oscillatory ventilation (HFOV) to conventional intermittent mandatory ventilation (CV) in the management of respiratory distress syndrome. Only premature neonates with a birth weight less than 1.751 kg were eligible for enrollment into the study. Of 83 patients studied, 26 patients were assigned to CV-only, 27 to HFOV for 72 hours followed by CV (HFOV/CV), and 30 to HFOV-only until extubation. There was no difference among the three groups with respect to the incidence of pulmonary airleak, intraventricular hemorrhage, or death. The highest incidence of chronic lung disease was in the CV-only group. Although both HFOV groups had a lower incidence of chronic lung disease assessed at 30 days and 36 weeks postconception age, the difference was statistically significant only between the CV-only and HFOV-only groups (65% vs 30% at 30 days; P = .008; 38% vs 10% at 36 weeks postconception age, P = .013). These results suggest that use of HFOV as the predominant mode of ventilation in the management of respiratory distress syndrome is as safe as CV and can contribute to a decreased incidence of chronic lung disease. Furthermore, a short (72-hour) period of HFOV support does not provide the same advantage as continuous HFOV.

Intraventricular hemorrhage and high-frequency ventilation: a meta-analysis of prospective clinical trials.

OBJECTIVE: The association between high-frequency ventilation (HFV) and intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) has been debated. PURPOSE: To determine if premature neonates treated with HFV are at greater risk for developing IVH and/or PVL than neonates treated with conventional ventilation, we completed a meta-analysis of all prospective randomized control trials comparing HFV and conventional ventilation in the management of respiratory distress syndrome. METHODS: The meta-analysis included nine studies comparing HFV and conventional ventilation in the management of preterm neonates. To summarize the data, we calculated the difference in absolute risk for IVH and PVL between neonates treated with HFV and those treated with standard ventilation. These differences were combined to determine an overall difference in the absolute risk and its confidence interval. We examined the effect of estimated gestational age, birth weight, surfactant, and age at study entry on the results. Because one trial (HIFI study) was much larger than the other studies, it dominated the analysis, so we evaluated the data with and without including data from the HIFI trial. RESULTS: The occurrences of IVH and PVL ranged from 14% to 47% and 5% to 16%, respectively. This variation may be explained by the difference in the populations of neonates treated. The meta-analysis showed that use of HFV was associated with an increased risk of PVL (odds ratio = 1.7 with a confidence interval of 1.06 to 2.74), but not IVH or severe (> or = grade 3) IVH. When the results of the HIFI study were excluded, there were no differences between HFV and conventional ventilation in the occurrence of IVH or PVL. CONCLUSIONS: The association between HFV and adverse neurologic outcomes is primarily influenced by the results of the HIFI trial. Meta-analysis of more recent studies does not confirm the findings of the HIFI trial and suggests that HFV is not associated with increased occurrence of IVH or PVL.

High-frequency oscillatory ventilation and extracorporeal membrane oxygenation for the treatment of acute neonatal respiratory failure.

Forty-six (92%) outborn and four (8%) inborn term or near-term neonates were admitted for extracorporeal membrane oxygenation (ECMO) treatment to a neonatal intensive care unit between July 1, 1985, and November 1, 1987. All infants had PAO2-PaO2 greater than or equal to 600 mm Hg in spite of aggressive conventional ventilatory and pharmacologic therapy. All patients were offered rescue treatment with high-frequency oscillatory ventilation (HFOV), and only if there was no improvement in PAO2-PaO2 with HFOV were infants treated using ECMO. Four patients died before receiving an adequate trial of HFOV and before emergency ECMO support could be initiated; 21 patients, all of whom survived to hospital discharge, responded to HFOV; 25 patients ultimately required ECMO therapy for cardiopulmonary support, with 22 (88%) surviving to discharge. Neonates responding to HFOV were of slightly younger gestational age (38 +/- 2 weeks vs 40 +/- 2 weeks, mean +/- SD; P less than .001) and more frequently had clinical evidence of pneumonia (11 of 21 vs 2 of 25; P less than .002). There was no statistically significant difference in outcome with respect to the number of ventilator days, hospital days, or survival between patients responding to HFOV and patients who required ECMO. Morbidity was increased in ECMO patients, with bleeding abnormalities, seizures, and renal failure occurring more frequently than in HFOV-treated infants. Overall, 92% (46 of 50) of the patients were treated with a staged protocol using HFOV before ECMO. A total of 46% (21 of 46) responded to HFOV treatment alone and did not require ECMO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.

OBJECTIVE: To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support. DESIGN: A prospective randomized clinical trial. SETTING: Three community-based level III neonatal intensive care units. SUBJECTS: A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50. INTERVENTIONS: Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit. MEASUREMENTS AND MAIN RESULTS: No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants. CONCLUSIONS: When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.

Role of lung injury in the pathogenesis of hyaline membrane disease in premature baboons.

To test the hypothesis that hyaline membrane disease (HMD) has a multifactorial etiology in which barotrauma plays a major role, we compared the immediate institution of high-frequency oscillatory ventilation (HFOV; 15 Hz, n = 5) with positive-pressure ventilation with positive end-expiratory pressure (PPV; n = 7) in premature baboons (140-days gestation) with HMD. Measurements of ventilation settings and physiological parameters were obtained and arterial-to-alveolar O2 (PaO2-to-PAO2) ratio and oxygenation index [(PaO2/PAO2)-to-mean airway pressure ratio (IO2)] were calculated. At death (24 h), static pressure-volume (PV) curves were performed, and phospholipids (PL) and platelet-activating factor (PAF) were measured in lung lavage fluid. Morphological inflation patterns were analyzed using a panel of standards. By design, mean airway pressure was initially higher (19 vs. 13 cmH2O) in the HFOV animals. PaO2-to-PAO2 ratio and IO2 progressively deteriorated in the PPV animals and then stabilized at significantly lower levels than with HFOV. PV curves from HFOV animals had significant increases in lung volume at maximum distending pressure, deflation volume at 10 cmH2O, and hysteresis area compared with PPV, which showed no hysteresis. Seven of seven PPV and only one of five HFOV animals had morphological findings of HMD. PL amount and composition in both groups were consistent with immaturity, even though the quantity was significantly greater in the PPV group. PAF was present (greater than or equal to 0.10 pmol) in six of seven PPV and in the only HFOV animal with HMD. We conclude that HFOV protected PL-deficient premature baboons from changes in gas exchange, lung mechanics, and morphology typical of HMD in this model.(ABSTRACT TRUNCATED AT 250 WORDS)