Atmospheric Carbon and Transport - America (ACT-America) Data Sets: Description, Management, and Delivery.

The ACT-America project is a NASA Earth Venture Suborbital-2 mission designed to study the transport and fluxes of greenhouse gases. The open and freely available ACT-America data sets provide airborne in situ measurements of atmospheric carbon dioxide, methane, trace gases, aerosols, clouds, and meteorological properties, airborne remote sensing measurements of aerosol backscatter, atmospheric boundary layer height and columnar content of atmospheric carbon dioxide, tower-based measurements, and modeled atmospheric mole fractions and regional carbon fluxes of greenhouse gases over the Central and Eastern United States. We conducted 121 research flights during five campaigns in four seasons during 2016-2019 over three regions of the US (Mid-Atlantic, Midwest and South) using two NASA research aircraft (B-200 and C-130). We performed three flight patterns (fair weather, frontal crossings, and OCO-2 underflights) and collected more than 1,140 h of airborne measurements via level-leg flights in the atmospheric boundary layer, lower, and upper free troposphere and vertical profiles spanning these altitudes. We also merged various airborne in situ measurements onto a common standard sampling interval, which brings coherence to the data, creates geolocated data products, and makes it much easier for the users to perform holistic analysis of the ACT-America data products. Here, we report on detailed information of data sets collected, the workflow for data sets including storage and processing of the quality controlled and quality assured harmonized observations, and their archival and formatting for users. Finally, we provide some important information on the dissemination of data products including metadata and highlights of applications of ACT-America data sets.

Reconciling Assumptions in Bottom-Up and Top-Down Approaches for Estimating Aerosol Emission Rates From Wildland Fires Using Observations From FIREX-AQ.

Accurate fire emissions inventories are crucial to predict the impacts of wildland fires on air quality and atmospheric composition. Two traditional approaches are widely used to calculate fire emissions: a satellite-based top-down approach and a fuels-based bottom-up approach. However, these methods often considerably disagree on the amount of particulate mass emitted from fires. Previously available observational datasets tended to be sparse, and lacked the statistics needed to resolve these methodological discrepancies. Here, we leverage the extensive and comprehensive airborne in situ and remote sensing measurements of smoke plumes from the recent Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) campaign to statistically assess the skill of the two traditional approaches. We use detailed campaign observations to calculate and compare emission rates at an exceptionally high-resolution using three separate approaches: top-down, bottom-up, and a novel approach based entirely on integrated airborne in situ measurements. We then compute the daily average of these high-resolution estimates and compare with estimates from lower resolution, global top-down and bottom-up inventories. We uncover strong, linear relationships between all of the high-resolution emission rate estimates in aggregate, however no single approach is capable of capturing the emission characteristics of every fire. Global inventory emission rate estimates exhibited weaker correlations with the high-resolution approaches and displayed evidence of systematic bias. The disparity between the low-resolution global inventories and the high-resolution approaches is likely caused by high levels of uncertainty in essential variables used in bottom-up inventories and imperfect assumptions in top-down inventories.

Intra-uterine growth restriction and increased risk of hypertension in adult life: a follow-up study of 50-year-olds.

OBJECTIVE: To compare blood pressure between 50-year-old adults who were born at term (37-42 weeks of gestation) with intra-uterine growth restriction (IUGR; birth weight <10th centile) and a control group of similar age born at term without IUGR (birth weight ≥10th centile). STUDY DESIGN: Controlled comparative study. METHODS: Participants included 232 men and women who were born at the Royal Maternity Hospital, Belfast, a large regional maternity hospital in Northern Ireland, between 1954 and 1956. One hundred and eight subjects who were born with IUGR were compared with 124 controls with normal birth weight for gestation. The main outcome measures were systolic and diastolic blood pressure at approximately 50 years of age, measured according to European recommendations. RESULTS: The IUGR group had higher systolic and diastolic blood pressure than the control group: 131.5 [95% confidence interval (CI) 127.9-135.1] vs 127.1 (95% CI 124.3-129.2) mmHg and 82.3 (95% CI 79.6-85.0) vs 79.0 (95% CI 77.0-81.0) mmHg, respectively. After adjustment for gender, the differences between the groups were statistically significant: systolic blood pressure 4.5 (95% CI 0.3-8.7) mmHg and diastolic blood pressure 3.4 (95% CI 0.2-6.5) mmHg (both P < 0.05). More participants in the IUGR group were receiving treatment for high blood pressure compared with the control group [16 (15%) vs 11 (9%)], although this was not statistically significant. The proportion of subjects with blood pressure >140/90 mmHg or currently receiving antihypertensive treatment was 45% (n = 49) for the IUGR group, and 31% (n = 38) for the control group (odds ratio 1.9, 95% CI 1.1-3.3). Adjustment for potential confounders made little difference. CONCLUSIONS: IUGR is associated with higher blood pressure at 50 years of age. Individuals born with IUGR should have regular blood pressure screening and early treatment as required. Hypertension remains underdiagnosed and undertreated in adult life.

A RCT of peer-mentoring for first-time mothers in socially disadvantaged areas (the MOMENTS Study).

OBJECTIVE: Interventions to reduce health inequalities for young children and their mothers are important: involving peers is recommended, but evidence of value for this approach is limited. The authors aimed to examine the effect of an innovative tailored peer-mentoring programme, based on perceived needs, for first-time mothers in socio-economically deprived communities. DESIGN: Randomised controlled trial; parallel qualitative study with purposive samples using semistructured interviews. SETTING: Socio-economically disadvantaged areas, Belfast. PARTICIPANTS: Primigravidae, aged 16-30 years, without significant co-morbidity. INTERVENTION: Peer-mentoring by a lay-worker fortnightly during pregnancy and monthly for the following year, tailored to participants' wishes (home visits/telephone contacts), additional to usual care. MAIN OUTCOME MEASURES: Infant psychomotor and mental development (Bayley Scales of Infant Development (BSID-II)) at 1 year, assessed by an observer blinded to group allocation. Mothers' health at 1 year postnatal (SF-36). RESULTS: Of 534 women invited, 343(64%) participated; 85%, with their children, completed outcome assessments (140 of 172 intervention; 152 of 171 controls). Intervention and control groups did not differ in BSID-II psychomotor (mean difference 1.64, 95% CI -0.94 to 4.21) or mental (-0.81, -2.78 to 1.16) scores, nor SF-36 physical functioning (-5.4, -11.6 to 0.7) or mental health (-1.8, -6.1 to 2.6). Women valued advice given in context of personal experience of child-rearing. Mentors gained health-related knowledge, personal skills and new employment opportunities. CONCLUSIONS: Despite possible longer-term social advantage, this peer-mentoring programme showed no benefit for infant development or maternal health at 1 year. Further rigorous evaluation of important outcomes of complex interventions promoting health for children in socially disadvantaged communities is warranted. TRIAL REGISTRATION NO: ISRCTN 55055030.

The use of surfactants in 2009.

Surfactant replacement therapy has been available for about 25 years, revolutionising neonatal respiratory care after its introduction in the 1980s. Along with antenatal steroids, surfactants improve survival for preterm babies and they are now recommended routinely as early in the course of respiratory distress syndrome (RDS) as possible. Prophylactic treatment, although appearing ideal, exposes some babies who might manage perfectly well on continuous positive airway pressure (CPAP) to intubation and ventilation, which may increase the risk of bronchopulmonary dysplasia. Recent studies attempt to determine the optimal balance between avoiding ventilation by using CPAP and giving surfactant in a timely fashion to babies with RDS. Surfactants are also used for conditions other than RDS, such as meconium aspiration, pulmonary haemorrhage and pneumonia, although the evidence base for their use in these indications is much weaker. Recently, surfactants have been used to deliver steroids directly to the lungs and this seems to be a promising technique worthy of further study. Finally, the quest goes on to develop a synthetic product that can match the effects of animal derived natural surfactants and could be produced at lower cost.

Treatment of asphyxiated newborns with moderate hypothermia in routine clinical practice: how cooling is managed in the UK outside a clinical trial.

BACKGROUND: This is a phase 4 study of infants registered with the UK TOBY Cooling Register from December 2006 to February 2008. The registry was established on completion of enrolLment to the TOBY randomised trial of treatment with whole body hypothermia following perinatal asphyxia at the end of November 2006. METHODS: We collected information about patient characteristics, condition at birth, resuscitation details, severity of encephalopathy, hourly temperature record, clinical complications and outcomes before hospital discharge. RESULTS: 120 infants born at a median of 40 (IQR 38-41) weeks' gestation and weighing a median of 3287 (IQR 2895-3710) g at birth were studied. Cooling was started at a median of 3 h 54 min (IQR 2 h-5 h 32 min) after birth. All but three infants underwent whole body cooling. The mean (SD) rectal temperature from 6 to 72 h of the cooling period was 33.57 degrees C (0.51 degrees C). The daily encephalopathy score fell: median (IQR) 11 (6-15), 9.7 (5-14), 8 (5-13) and 7 (2-12) on days 1-4 after birth, respectively. 51% of the infants established full oral feeding at a median (range) of 9 (4-24) days. 26% of the study infants died. MRI was consistent with hypoxia-ischaemia in most cases. Clinical complications were not considered to be due to hypothermia. CONCLUSION: In the UK, therapeutic hypothermia following perinatal asphyxia is increasingly being provided. The target body temperature is successfully achieved and the clinical complications observed were not attributed to hypothermia. Treatment with hypothermia may have prevented the worsening of the encephalopathy that is commonly observed following asphyxia.

[EuroNeoStat: a European information system on the outcomes of care for very-low-birth-weight infants (< 1500 g)]. / EuroNeoStat: ein Europäisches Informationssystem zur erfassung der behandlungsergebnisse von sehr untergewichtigen Frühgeborenen mit einem Geburtsgewicht < 1500 g.

BACKGROUND: Prematurity rates are increasing throughout the world. Despite an overall rather small percentage of very low birth weight infants (VLBWI), which is approx. 1-2 % in most countries, these infants contribute significantly to morbidity and neonatal and infant mortality rates. METHODS: EuroNeoStat was initiated as an European information system on the outcomes of VLBWI to monitor and improve the care of these infants throughout Europe. EuroNeoStat includes an initiative, called EuroNeoSafe, to promote the safety of these high risk preterm infants. Perinatal and neonatal data from VLBWI is collected without using data that identify individuals or institutions. These data is analyzed at the coordination center in Bilbao. All institutions taking care on VLBWI in Europe can participate in this network and will be able to compare their own outcome data with other institutions from the network. Information on EuroNeoStat and the current data set is available on www.euroneostat.org. CONCLUSION: Successful initiatives aiming at improving outcomes in perinatal and neonatal care require collaborative networking, an attitude of constructive criticism and thorough comparative analysis of the outcomes and incidents in the health-care process.

Surfactants: past, present and future.

In 1929 Kurt von Neergaard performed experiments suggesting the presence of pulmonary surfactant and its relevance to the newborn's first breath. Almost 25 years later, Richard Pattle, John Clements and Chris Macklin, each working on the effects of nerve gases on the lungs, contributed to the understanding of the physiology of pulmonary surfactant. About 5 years later Mary Ellen Avery and Jere Mead published convincing evidence that preterm neonates dying of hyaline membrane disease (respiratory distress syndrome, RDS) had a deficiency of pulmonary surfactant. The first trials of nebulized synthetic (protein-free) surfactant to prevent RDS were published soon after Patrick Bouvier Kennedy (son of President John F Kennedy) died of this disorder after treatment in Boston. These trials were unsuccessful; however, Goran Enhorning and Bengt Robertson in the early 1970s demonstrated that natural surfactants (containing proteins) were effective in an immature rabbit model of RDS. Soon after this Forrest Adams showed that a natural surfactant was also effective in an immature lamb model. Working with him was Tetsuro Fujiwara who 2 years later, after returning to Japan, published the seminal article reporting the responses of 10 preterm infants with RDS to a bolus of modified bovine surfactant. During the 1980s there were numerous randomized controlled trials of many different natural and synthetic surfactants, demonstrating reductions in pulmonary air leaks and neonatal mortality. Subsequently natural surfactants were shown to be superior to the protein-free synthetic products. Recently there have been a number of randomized trials comparing different natural surfactant preparations. Commercially available bovine surfactants may have similar efficacy but there is some evidence that a porcine surfactant used to treat RDS with an initial dose of 200 mg per kg is more effective than a bovine surfactant used in an initial dose of 100 mg per kg. Bovine and porcine surfactants have not been compared in trials of prophylaxis. Very recently a new synthetic surfactant with a surfactant protein mimic has been compared with other commercially available natural and synthetic surfactants in two trials. The new surfactant may be superior to one of the older protein-free synthetic surfactants but there is no evidence of its superiority over established natural products and it is currently not approved for clinical use. A number of other new synthetic surfactants have been tested in animal models or in treatment of adults with ARDS, but so far there have been no reports of treatment of neonatal RDS. Natural surfactants work best if given by a rapid bolus into the lungs but less invasive methods such as a laryngeal mask, pharyngeal deposition or rapid extubation to CPAP have showed promise. Unfortunately, delivery of surfactant by nebulization has so far been ineffective. Surfactant treatment has been tried in a number of other neonatal respiratory disorders but only infants with meconium aspiration seem to benefit although larger and more frequent doses are probably needed to demonstrate improved lung function. A surfactant protocol based upon early treatment and CPAP is suggested for very preterm infants. Earlier treatment may improve survival rates for these infants; however, there is a risk of increasing the prevalence of milder forms of chronic lung disease. Nevertheless, surfactant therapy has been a major contribution to care of the preterm newborn during the past 25 years.

Interventions to prevent hypothermia at birth in preterm and/or low birthweight infants.

BACKGROUND: Hypothermia incurred during routine postnatal resuscitation is a world-wide issue (across all climates), associated with morbidity and mortality. Keeping vulnerable preterm infants warm is problematic even when recommended routine thermal care guidelines are followed in the delivery suite. OBJECTIVES: To assess efficacy and safety of interventions designed for prevention of hypothermia in preterm and/or low birthweight infants applied within ten minutes after birth in the delivery suite compared with routine thermal care. SEARCH STRATEGY: The standard search strategy of The Cochrane Collaboration was followed. Electronic databases were searched: MEDLINE (1966 to July Week 4 2007 ), CINAHL (1982 to July Week 4 2007), EMBASE (1974 to 01/08/2007), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), Database of Abstracts of Reviews of Effects (DARE 1994 to July 2007), conference/symposia proceedings using ZETOC (1993 to 17/08/2007), ISI proceedings (1990 to 17/08/2007) and OCLC WorldCat (July 2007). Identified articles were cross-referenced. No language restrictions were imposed. SELECTION CRITERIA: All trials using randomised or quasi-randomised allocations to test a specific intervention designed to prevent hypothermia, (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery suite to infants of < 37 weeks' gestational age or birthweight

Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates.

BACKGROUND: Chronic lung disease remains a common complication among preterm infants. There is increasing evidence that inflammation plays an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties, corticosteroids are an attractive intervention strategy. However, there are growing concerns regarding short and long-term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects. OBJECTIVES: To determine the impact of inhaled corticosteroids administered to ventilated very low birth weight preterm neonates in the first two weeks of life for the prevention of chronic lung disease (CLD). SEARCH STRATEGY: Randomized and quasi-randomized trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - July 2007), EMBASE (1980 - July 2007), CINAHL (1982 - July 2007), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web-site (1990 - April 2007). SELECTION CRITERIA: Randomized controlled trials of inhaled corticosteroid therapy initiated within the first 2 weeks of life in ventilated preterm infants with birth weight <1500 grams were included in this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including chronic lung disease at 28 days or 36 weeks postmenstrual age (PMA), mortality, combined outcome of death or CLD at 28 days of age and at 36 weeks PMA, the need for systemic corticosteroids, failure to extubate within 14 days and adverse effects of corticosteroids were evaluated. All data were analyzed using RevMan 4.2.10. When possible, meta-analysis was performed using relative risk (RR), risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, the number needed to treat (NNT) was calculated. MAIN RESULTS: Three additional trials were identified for inclusion in this update. Eleven trials assessing the impact of inhaled corticosteroid for the prevention of CLD were identified. Four trials were excluded. The present review includes data analyses based on seven qualifying trials. There was no statistically significant effect of inhaled steroids on CLD either at 28 days [typical RR 1.05 (95% CI 0.84, 1.32); typical RD 0.02 (95% CO -0.07, 0.11)] or at 36 weeks PMA [typical RR 0.97 (95% CI 0.62, 1.52); typical RD 0.00 (95% CI -0.07, 0.06)], when analyzed either for all randomized infants or among survivors. No statistically significant differences were noted for mortality or for the combined outcome of mortality and CLD either at 28 days of age or at 36 weeks PMA. There were no statistically significant differences in adverse events between groups. AUTHORS' CONCLUSIONS: Based on this updated review, there is no evidence from the trials reviewed that early administration (in the first two weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.

Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm infants.

BACKGROUND: Chronic lung disease (CLD) remains a serious and common problem among very low birth weight infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent CLD. However, the use of systemic steroids has been associated with serious short and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract might result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects. OBJECTIVES: To determine the effect of inhaled versus systemic corticosteroids administered to ventilator dependent preterm neonates with birth weight < 1500 g or gestational age < 32 weeks after two weeks of life for the treatment of evolving CLD. SEARCH STRATEGY: Randomized and quasi-randomized trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - June 2007), EMBASE (1980 - June 2007), CINAHL (1982 - June 2007), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies website (1990 - April 2007). SELECTION CRITERIA: Randomized or quasi-randomized trials comparing inhaled versus systemic corticosteroid therapy (irrespective of the dose and duration of therapy) starting after the first two weeks of life in ventilator dependent very low birth weight preterm infants. DATA COLLECTION AND ANALYSIS: Data were extracted regarding clinical outcomes including CLD at 28 days or 36 weeks postmenstrual age (PMA), mortality, combined outcome of death or CLD at 28 days of age or 36 weeks PMA, other pulmonary outcomes and adverse effects. All data were analyzed using RevMan 4.2.10. When appropriate, meta-analysis was performed using relative risk (RR), risk difference (RD), and weighted mean difference (WMD) along with their 95% confidence intervals (CI). If RD was statistically significant, the number needed to treat (NNT) was calculated. MAIN RESULTS: Data from one additional trial were available for inclusion in this update. Thus, five trials comparing inhaled versus systemic corticosteroids in the treatment of CLD were identified. Two trials were excluded as both included non-ventilator dependent patients and three trials qualified for inclusion in this review. Halliday et al (Halliday 2001) randomized infants at < 72 hours, while Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) randomized at 12 - 21 days. The data from the two trials of Rozycki et al and Suchmoski et al are combined using meta-analytic techniques. The data from the trial by Halliday et al are reported separately, as outcomes were measured over different time periods from the age at randomization. In none of the trials was there a statistically significant difference between the groups in the incidence of CLD at 36 weeks PMA among all randomized infants. The estimates for the trial by Halliday et al (Halliday 2001) were RR 1.10 (95% CI 0.82, 1.47), RD 0.03 (95% CI -0.08, 0.15); number of infants (n = 292). For the trials by Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) the typical RR was 1.02 (95% CI 0.83, 1.25) and the typical RD 0.01 (95% CI -0.11, 0.14); (number of infants = 139 ). There were no statistically significant differences between the groups in either trial for oxygen dependency at 28 days of age, death by 28 days or 36 weeks PMA, the combined outcome of death by or CLD at 28 days or 36 weeks PMA, duration of intubation, duration of oxygen dependence, or adverse effects. Information on the long-term neurodevelopmental outcomes was not available. AUTHORS' CONCLUSIONS: This review found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator dependent preterm infants. Neither inhaled steroids nor systemic steroids can be recommended as standard treatment for ventilated preterm infants. There was no evidence of difference in effectiveness or side-effect profiles for inhaled versus systemic steroids. A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing side-effects. To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcome, should be addressed in future studies.

Neonatal ventilation with inhaled nitric oxide vs. ventilatory support without inhaled nitric oxide for infants with severe respiratory failure born at or near term: the INNOVO multicentre randomised controlled trial.

BACKGROUND: Evidence from European centres to support the use of nitric oxide (NO) in mature newborns with evidence of severe respiratory failure is sparse. METHODS: Infants of >33 weeks' gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomised to receive or not to receive inhaled NO (iNO). The study was not blinded. RESULTS: Sixty infants were recruited (29 allocated iNO, 31 no iNO) from 15 neonatal units in the UK, Finland, Belgium and the Republic of Ireland. 15/60 recruited babies died, and 8.1% of the survivors (4/45) were classified as severely disabled at 1 year. There was no statistically significant difference between the randomised groups in terms of the primary outcome of death or severe disability by the corrected age of 1 year (relative risk = 0.96 (95% confidence interval = 0.46-2.03); p = 0.86) (Fisher's exact p = 1.00). The costs of NO were outweighed by reduced extra corporeal membrane oxygenation costs in the iNO group. The mean total hospitalisation costs were lower in the iNO group, although the mean difference (1,697 pounds) was not statistically significant (95% confidence interval = -14,472 to 11,478). CONCLUSIONS: The results complement those of previous studies that suggest NO is cost-effective and reduces the need for extra corporeal membrane oxygenation in this group of babies. Overall survival rates compare unfavourably with results of US trials.

A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses. AIM: To determine whether a dose-response relationship existed for iNO in preterm infants. DESIGN: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. SUBJECTS: Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited. OUTCOME MEASURE: A clinically significant dose-response was defined as a rise in the post-ductal arterial oxygen tension (PaO(2)) of at least 3 kPa. RESULTS: Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified (likelihood ratio test, p=0.34). CONCLUSION: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.