Compared with specialist registrars, experienced staff nurses shorten the duration of weaning neonates from mechanical ventilation

OBJECTIVE: To compare the overall performance of specially trained neonatal nurses acting autonomously, unsupervised, and without a protocol with specialist registrars when weaning neonates from mechanical ventilation.

DESIGN: Prospective, randomized, controlled trial.

SETTING: A single neonatal intensive care unit.

PATIENTS: Neonates requiring conventional mechanical ventilation (n = 50).

INTERVENTIONS: Infants on conventional ventilation were randomly assigned to receive either nurse-led (n = 25) or registrar-led (n = 23) weaning. A total of 48 infants completed the study (two infants in the registrar group were excluded when their parents withdrew consent).

MEASUREMENTS AND MAIN RESULTS: The main outcome measure, median weaning time, was 1200 mins (95% confidence interval [CI], 621-1779 mins) in the nurse group and 3015 mins (95% CI, 2650-3380 mins) in the registrar group (p = .0458). The median time from treatment assignment to the first ventilator change was 60 mins (95% CI, 52-68 mins) in the nurse group and 120 mins (95% CI, 103-137 mins) in the registrar group (p = .35). On average, the nurses made ventilator changes every 4.5 hrs (95% CI, 2.9-6 hrs) and the registrars every 7.2 hrs (95% CI, 5.4-9 hrs; p = .003). The median number (range) of backward steps taken per infant was 0 (0-5 steps) in the nurse group and 1 (0-5 steps) in the registrar group (p = .019).

CONCLUSIONS: The findings of this study suggest that additional domains of neonatal critical care could be reviewed for their potential transfer to appropriately prepared nurses.

Non-invasive Ventilation of Patients with ARDS: Insights from the LUNG SAFE Study

Background: Non-invasive ventilation (NIV) is increasingly used in patients with Acute Respiratory Distress Syndrome (ARDS). Whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful is unknown. The evidence supporting NIV use in patients with ARDS remains relatively sparse.

Methods: The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study described the management of patients with ARDS. This sub-study examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV and the impact of NIV on outcome.

Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and Intensive Care Unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1 % and 45.4%, respectively. NIV use was independently associated with increased ICU (HR 1.446; [1.159-1.805]), but not hospital mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mmHg.

Conclusions: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV appears to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mmHg.

Trial Registration: ClinicalTrials.gov NCT02010073

Cross-validation of geo-electrical and hydrogeological models to evaluate seawater intrusion in coastal aquifers

The validation of variable-density flow models simulating seawater intrusion in coastal aquifers requires information about concentration distribution in groundwater. Electrical resistivity tomography (ERT) provides relevant data for this purpose. However, inverse modeling is not accurate because of the non-uniqueness of solutions. Such difficulties in evaluating seawater intrusion can be overcome by coupling geophysical data and groundwater modeling. First, the resistivity distribution obtained by inverse geo-electrical modeling is established. Second, a 3-D variable-density flow hydrogeological model is developed. Third, using Archie's Law, the electrical resistivity model deduced from salt concentration is compared to the formerly interpreted electrical model. Finally, aside from that usual comparison-validation, the theoretical geophysical response of concentrations simulated with the groundwater model can be compared to field-measured resistivity data. This constitutes a cross-validation of both the inverse geo-electrical model and the groundwater model.
[Comte, J.-C., and O. Banton (2007), Cross-validation of geo-electrical and hydrogeological models to evaluate seawater intrusion in coastal aquifers, Geophys. Res. Lett., 34, L10402, doi:10.1029/2007GL029981.]

The impedance cardiogram recorded through two electrocardiogram/defibrillator pads as a determinant of cardiac arrest during experimental studies

OBJECTIVE: Laypersons are poor at emergency pulse checks (sensitivity 84%, specificity 36%). Guidelines indicate that pulse checks should not be performed. The impedance cardiogram (dZ/dt) is used to assess stroke volume. Can a novel defibrillator-based impedance cardiogram system be used to distinguish between circulatory arrest and other collapse states?

DESIGN: Animal study.

SETTING: University research laboratory.

SUBJECTS: Twenty anesthetized, mechanically ventilated pigs, weight 50-55 kg.

INTERVENTIONS: Stroke volume was altered by right ventricular pacing (160, 210, 260, and 305 beats/min). Cardiac arrest states were then induced: ventricular fibrillation (by rapid ventricular pacing) and, after successful defibrillation, pulseless electrical activity and asystole (by high-dose intravenous pentobarbitone).

MEASUREMENTS AND MAIN RESULTS: The impedance cardiogram was recorded through electrocardiogram/defibrillator pads in standard cardiac arrest positions. Simultaneously recorded electro- and impedance cardiogram (dZ/dt) along with arterial blood pressure tracings were digitized during each pacing and cardiac arrest protocol. Five-second epochs were analyzed for sinus rhythm (20 before ventricular fibrillation, 20 after successful defibrillation), ventricular fibrillation (40), pulseless electrical activity (20), and asystole (20), in two sets of ten pigs (ten training, ten validation). Standard impedance cardiogram variables were noncontributory in cardiac arrest, so the fast Fourier transform of dZ/dt was assessed. During ventricular pacing, the peak amplitude of fast Fourier transform of dZ/dt (between 1.5 and 4.5 Hz) correlated with stroke volume (r2 = .3, p < .001). In cardiac arrest, a peak amplitude of fast Fourier transform of dZ/dt of < or = 4 dB x ohm x rms indicated no output with high sensitivity (94% training set, 86% validation set) and specificity (98% training set, 90% validation set).

CONCLUSIONS: As a powerful clinical marker of circulatory collapse, the fast Fourier transformation of dZ/dt (impedance cardiogram) has the potential to improve emergency care by laypersons using automated defibrillators.

Geotechnical monitoring using a combination of LIDAR, real-time dGPS, and electrical tomography to assess geotechnical risk of a coastal landslide.

The Antrim Coast Road stretching from the seaport of Larne in the East of Northern Ireland has a well-deserved reputation for being one of the most spectacular roads in Europe (Day, 2006). However the problematic geology; Jurassic Lias Clay and Triassic Mudstone overlain by Cretaceous Limestone and Tertiary Basalt, and environmental variables result in frequent instances of slope instability manifested in both shallow debris flows and occasional massive rotational movements, creating a geotechnical risk to this highway. This paper describes how a variety of techniques are being used to both assess instability and monitor movement of these active slopes near one site at Straidkilly Point, Glenarm. An in-depth understanding of the geology was obtained via boreholes, resistivity surveys and laboratory testing. Environmental variables recorded by an on-site weather station were correlated with measured pore water pressure and soil moisture infiltration data. Terrestrial LiDAR (TLS), with surveys carried out on a bi-monthly basis allowed for the generation of Digital Elevation Models (DEMs) of difference, highlighting areas of recent movement, accumulation and depletion. Morphology parameters were generated from the DEMs and include slope, curvature and multiple measures of roughness. Changes in the structure of the slope coupled with morphological parameters were characterised and linked to progressive failures from the temporal monitoring. In addition to TLS monitoring, Aerial LiDAR datasets were used for the spatio-morphological characterisation of the slope on a macro scale. A Differential Global Positioning System (dGPS) was also deployed on site to provide a real-time warning system for gross movements, which were also correlated with environmental conditions. Frequent electrical resistivity tomography (ERT) surveys were also implemented to provide a better understanding of long-term changes in soil moisture and help to define the complex geology. The paper describes how the data obtained via a diverse range of methods has been combined to facilitate a more informed management regime of geotechnical risk by the Northern Ireland Roads Service.

Eradication of endotracheal tube biofilm by nebulised gentamicin.

Objective: To compare the efficacy of gentamicin, nebulised via the endotracheal tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in preventing the formation of ET biofilm.

Setting: General intensive care units in two university teaching hospitals.

Design: The microbiology of ET biofilm from 36 ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and trough tracheal concentrations of gentamicin, cefotaxime or cefuroxime were measured in each patient group, on the 2nd day of intubation.

Patients: Twelve patients received gentamicin (80 mg) nebulised in 4 ml normal saline every 8 h, 12 cefotaxime (1 g, 12 hourly) and 12 cefuroxime (750 mg, 8 hourly). Prophylaxis was continued for the duration of intubation.

Measurements and results: Samples of tracheal secretions were taken on the 2nd day of ventilation for determination of antibiotic concentrations. Following extubation, ETs were examined for the presence of biofilm. Pathogens considered to be common aetiological agents for VAP included Staphylococcus aureus, enterococci, Enterobacteriaceae and pseudomonads. While microbial biofilm was found on all ETs from the cephalosporin group, microbial biofilm of these micro-organisms was found on 7 of the 12 ET tubes from patients receiving cefotaxime [S. aureus (4), pseudomonads (1), Enterobacteriaceae (1), enterococcus (1)] and 8 of the 12 ET tubes from patients receiving cefuroxime [Enterobacteriaceae (6), P. aeruginosa (1) and enterococcus (1)]. While microbial biofilm was observed on five ETs from patients receiving nebulised gentamicin, none of these were from pathogens for ventilator-associated pneumonia (VAP). Tracheal concentrations of both cephalosporins were lower than those needed to inhibit the growth of pathogens recovered from ET tube biofilm. The median (and range) concentrations for cefotaxime were 0.90 (<0.23–1.31) mg/l and 0.28 (<0.23–0.58) mg/l for 2 h post-dose and trough samples, respectively. Two hours post-dose concentrations of cefuroxime (median and range) were 0.40 (0.34–0.83) mg/l, with trough concentrations of 0.35 (<0.22–0.47) mg/l. Tracheal concentrations (median and range) of gentamicin measured 1 h post-nebulisation were 790 (352–>1250) mg/l and then, before the next dose, were 436 (250–1000) mg/l.

Conclusion: Nebulised gentamicin attained high concentrations in the ET lumen and was more effective in preventing the formation of biofilm than either parenterally administered cephalosporin and therefore may be effective in preventing this complication of mechanical ventilation.

A Multicenter, Randomised Open Study of Early Corticosteroid Treatment (OSECT) in Preterm Infants With Respiratory Illness: Comparison of Early and Late Treatment and of Dexamethasone and Inhaled Budesonide

AIM: To compare early (15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease. METHODS: Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age 30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily. RESULTS: There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance. CONCLUSIONS: Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective

Cyclin G associated kinase interacts with interleukin 12 receptor beta2 and suppresses interleukin 12 induced IFN-gamma production.

BACKGROUND: Although severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation (NPPV), increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure, especially hypercapnic acute respiratory failure (HARF). To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy, a prospective case-control study was conducted at a university respiratory intensive care unit (RICU) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) during the past 3 years. METHODS: Forty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups, which were carefully matched for age, sex, COPD course, tobacco use and previous hospitalization history, according to the severity of encephalopathy, 22 patients with Glasgow coma scale (GCS) <10 served as group A and 21 with GCS = 10 as group B. RESULTS: Compared with group B, group A had a higher level of baseline arterial partial CO2 pressure ((102 +/- 27) mmHg vs (74 +/- 17) mmHg, P <0.01), lower levels of GCS (7.5 +/- 1.9 vs 12.2 +/- 1.8, P <0.01), arterial pH value (7.18 +/- 0.06 vs 7.28 +/- 0.07, P <0.01) and partial O(2) pressure/fraction of inspired O(2) ratio (168 +/- 39 vs 189 +/- 33, P <0.05). The NPPV success rate and hospital mortality were 73% (16/22) and 14% (3/22) respectively in group A, which were comparable to those in group B (68% (15/21) and 14% (3/21) respectively, all P > 0.05), but group A needed an average of 7 cm H2O higher of maximal pressure support during NPPV, and 4, 4 and 7 days longer of NPPV time, RICU stay and hospital stay respectively than group B (P <0.05 or P <0.01). NPPV therapy failed in 12 patients (6 in each group) because of excessive airway secretions (7 patients), hemodynamic instability (2), worsening of dyspnea and deterioration of gas exchange (2), and gastric content aspiration (1). CONCLUSIONS: Selected patients with severe hypercapnic encephalopathy secondary to HARF can be treated as effectively and safely with NPPV as awake patients with HARF due to AECOPD; a trial of NPPV should be instituted to reduce the need of endotracheal intubation in patients with severe hypercapnic encephalopathy who are otherwise good candidates for NPPV due to AECOPD.

Type XVIII collagen degradation products in acute lung injury

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge.

A randomized clinical trial of hydroxymethylglutaryl-Coenzyme A reductase inhibition for Acute Lung Injury (The HARP study)

Rationale: There is no effective pharmacological treatment for acute lung injury (ALI). Statins are a potential new therapy because they modify many of the underlying processes important in ALI.

Objectives: To test whether simvastatin improves physiological and biological outcomes in ALI.

Methods: We conducted a randomized, double-blinded, placebo-controlled trial in patients with ALI. Patients received 80 mg simvastatin or placebo until cessation of mechanical ventilation or up to 14 days. Extravascular lung water was measured using thermodilution. Measures of pulmonary and nonpulmonary organ function were assessed daily. Pulmonary and systemic inflammation was assessed by bronchoalveolar lavage fluid and plasma cytokines. Systemic inflammation was also measured by plasma C-reactive protein.

Measurements and Main Results: Sixty patients were recruited. Baseline characteristics, including demographics and severity of illness scores, were similar in both groups. At Day 7, there was no difference in extravascular lung water. By Day 14, the simvastatin-treated group had improvements in nonpulmonary organ dysfunction. Oxygenation and respiratory mechanics improved, although these parameters failed to reach statistical significance. Intensive care unit mortality was 30% in both groups. Simvastatin was well tolerated, with no increase in adverse events. Simvastatin decreased bronchoalveolar lavage IL-8 by 2.5-fold (P = 0.04). Plasma C-reactive protein decreased in both groups but failed to achieve significance in the placebo-treated group.

Conclusions: Treatment with simvastatin appears to be safe and may be associated with an improvement in organ dysfunction in ALI. These clinical effects may be mediated by a reduction in pulmonary and systemic inflammation.

Evaluation of effective groundwater recharge of freshwater lens in small islands by the combined modeling of geoelectrical data and water heads

In small islands, a freshwater lens can develop due to the recharge induced by rain. Magnitude and spatial distribution of this recharge control the elevation of freshwater and the depth of its interface with salt water. Therefore, the study of lens morphology gives useful information on both the recharge and water uptake due to evapotranspiration by vegetation. Electrical resistivity tomography was applied on a small coral reef island, giving relevant information on the lens structure. Variable density groundwater flow models were then applied to simulate freshwater behavior. Cross validation of the geoelectrical model and the groundwater model showed that recharge exceeds water uptake in dunes with little vegetation, allowing the lens to develop. Conversely, in the low-lying and densely vegetated sectors, where water uptake exceeds recharge, the lens cannot develop and seawater intrusion occurs. This combined modeling method constitutes an original approach to evaluate effective groundwater recharge in such environments.
[Comte, J.-C., O. Banton, J.-L. Join, and G. Cabioch (2010), Evaluation of effective groundwater recharge of freshwater lens in small islands by the combined modeling of geoelectrical data and water heads, Water Resour. Res., 46, W06601, doi:10.1029/2009WR008058.]

Relationship between electrical resistivity and basic geotechnical parameters for marine clays

Recently, considerable efforts have been made in the attempt to map quick clay areas using electrical resistivity measurements. However there is a lack of understanding regarding which soil parameters control the measured resistivity values. To address this issue, inverted resistivity values from 15 marine clay sites in Norway have been compared with basic geotechnical index properties. It was found that the resistivity value is strongly controlled by the salt content of the pore fluid. Resistivity decreases rapidly with increasing salt content. There is also a relatively clear trend of decreasing resistivity with increasing clay content and plasticity index. Resistivity values become very low (˜5 O·m) for high clay content (>50%), medium- to high-plasticity (Ip ˜ 20%) materials with salt content values greater than about 8 g/L (or corresponding remoulded shear strength values greater than 4 kPa). For the range of values studied, there is poor correlation between resistivity and bulk density and between resistivity and water content. The data studied suggest that the range of resistivity values corresponding to quick clay is 10 to 100 O·m, which is consistent with other published limits. A comparison is made between two-dimensional electrical resistivity tomography (ERT) and resistivity cone penetration test (RCPTU) data for two of the sites and the two sets of data show similar trends and values irrespective of scale effect.

Frequency and distribution of group I intron genotypes of Candida albicans colonising critically ill patients

A study is performed to examine the distribution and frequency of 25S rRNA intron genotypes of Candida albicans isolated from different anatomical sites of patients in an intensive care unit (ICU) setting. Germ-tube positive Candida isolates (n=65) from 65 patients are included and isolates are characterised by 25S intron genotyping, whereby all can be subdivided into four genotypes (A-D). Results demonstrated that there were no significant differences between the frequency and genotype distribution of the Candida isolates and the anatomical site of colonisation. Furthermore, analysis of the transposable intron region in the 25S rRNA gene demonstrated equal distribution, regardless of age and anatomical site of isolation (groin, throat, etc.). Therefore, there does not appear to be any selective pressure associated with any anatomical site, resulting in an ecological shift in the frequency of genotypes present. This suggests that C. albicans intron genotypes equally colonise those sites of the body examined in this study. Although such an ecological finding as this is interesting, it perpetuates the continued need to find a genotypic typing scheme that helps to identify the source (nosocomial or endogenous) and mode of entry of C. albicans into patients in the ICU setting, resulting in C. albicans bloodstream infection.

Assessment of the impedance cardiogram recorded by an automated external defibrillator during clinical cardiac arrest

OBJECTIVE: To assess the impedance cardiogram recorded by an automated external defibrillator during cardiac arrest to facilitate emergency care by lay persons. Lay persons are poor at emergency pulse checks (sensitivity 84%, specificity 36%); guidelines recommend they should not be performed. The impedance cardiogram (dZ/dt) is used to indicate stroke volume. Can an impedance cardiogram algorithm in a defibrillator determine rapidly circulatory arrest and facilitate prompt initiation of external cardiac massage?

DESIGN: Clinical study.

SETTING: University hospital.

PATIENTS: Phase 1 patients attended for myocardial perfusion imaging. Phase 2 patients were recruited during cardiac arrest. This group included nonarrest controls.

INTERVENTIONS: The impedance cardiogram was recorded through defibrillator/electrocardiographic pads oriented in the standard cardiac arrest position.

MEASUREMENTS AND MAIN RESULTS: Phase 1: Stroke volumes from gated myocardial perfusion imaging scans were correlated with parameters from the impedance cardiogram system (dZ/dt(max) and the peak amplitude of the Fast Fourier Transform of dZ/dt between 1.5 Hz and 4.5 Hz). Multivariate analysis was performed to fit stroke volumes from gated myocardial perfusion imaging scans with linear and quadratic terms for dZ/dt(max) and the Fast Fourier Transform to identify significant parameters for incorporation into a cardiac arrest diagnostic algorithm. The square of the peak amplitude of the Fast Fourier Transform of dZ/dt was the best predictor of reduction in stroke volumes from gated myocardial perfusion imaging scans (range = 33-85 mL; p = .016). Having established that the two pad impedance cardiogram system could detect differences in stroke volumes from gated myocardial perfusion imaging scans, we assessed its performance in diagnosing cardiac arrest. Phase 2: The impedance cardiogram was recorded in 132 "cardiac arrest" patients (53 training, 79 validation) and 97 controls (47 training, 50 validation): the diagnostic algorithm indicated cardiac arrest with sensitivities and specificities (+/- exact 95% confidence intervals) of 89.1% (85.4-92.1) and 99.6% (99.4-99.7; training) and 81.1% (77.6-84.3) and 97% (96.7-97.4; validation).

CONCLUSIONS: The impedance cardiogram algorithm is a significant marker of circulatory collapse. Automated defibrillators with an integrated impedance cardiogram could improve emergency care by lay persons, enabling rapid and appropriate initiation of external cardiac massage.

Neonatal pain in relation to postnatal growth in infants born very preterm

Procedural pain is associated with poorer neurodevelopment in infants born very preterm (= 32 weeks gestational age), however, the etiology is unclear. Animal studies have demonstrated that early environmental stress leads to slower postnatal growth; however, it is unknown whether neonatal pain-related stress affects postnatal growth in infants born very preterm. The aim of this study was to examine whether greater neonatal pain (number of skin-breaking procedures adjusted for medical confounders) is related to decreased postnatal growth (weight and head circumference [HC] percentiles) early in life and at term-equivalent age in infants born very preterm. Participants were n=78 preterm infants born = 32 weeks gestational age, followed prospectively since birth. Infants were weighed and HC measured at birth, early in life (median: 32 weeks [interquartile range 30.7-33.6]) and at term-equivalent age (40 weeks [interquartile range 38.6-42.6]). Weight and HC percentiles were computed from sex-specific British Columbia population-based data. Greater neonatal pain predicted lower body weight (Wald ?(2)=7.36, P=0.01) and HC (Wald ?(2)=4.36, P=0.04) percentiles at 32 weeks postconceptional age, after adjusting for birth weight percentile and postnatal risk factors of illness severity, duration of mechanical ventilation, infection, and morphine and corticosteroid exposure. However, later neonatal infection predicted lower weight percentile at term (Wald ?(2)=5.09, P=0.02). Infants born very preterm undergo repetitive procedural pain during a period of physiological immaturity that appears to impact postnatal growth, and may activate a downstream cascade of stress signaling that affects later growth in the neonatal intensive care unit.