Persisting hypoxaemia is an insufficient measure of adverse lung function in very immature infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD), defined as protracted neonatal hypoxaemia, is considered a risk factor for respiratory disease in adulthood. The relationship between this diagnosis and the actual lung injury appearing in very immature infants is, however, unknown. OBJECTIVES: To compare lung function at term in very immature infants and full-term infants, and to determine how degree and duration of neonatal hypoxaemia are related to other aspects of lung function. DESIGN AND METHODS: All surviving, consecutive infants with gestational age below 28 weeks from a geographically defined area were eligible. The alveolar-arterial oxygen pressure difference was assessed as a measure of oxygenation failure. At term, functional residual capacity and gas-mixing efficiency were measured by multiple-breath nitrogen washout, and compliance and conductance of the respiratory system by the occlusion method. The results were compared to those in 50 full-term controls. MAIN RESULTS: Thirty-seven of 46 eligible infants were included. The preterm infants differed markedly from the full-term infants in all lung functions tested. Infants diagnosed as having BPD had more compromised lung function than those without, but the latter group differed markedly from the full-term group in functional residual capacity, compliance and gas-mixing efficiency. Only the mechanical variables were correlated to hypoxaemia at 36 weeks postmenstrual age (PMA). CONCLUSIONS: Infants with gestational age below 28 weeks at birth have remarkably impaired lung function at term, regardless of whether they carry the diagnosis BPD or not. All very immature infants may be at risk of future respiratory disease and should be monitored appropriately.

Cardio-respiratory response to moderate chloral hydrate sedation in young lambs.

AIM: Chloral hydrate (CH) is the most commonly used sedative for medical procedures and lung function tests in infancy. The aim was to determine whether moderate CH sedation affects airway function, lung volume and ventilation. METHODS: Thirteen chronically instrumented 7- to 8-week-old lambs were studied both before and after CH sedation (50 mg/kg as intravenous bolus followed by 25 mg/kg/hour as continuous infusion). Nitrogen washout technique and lung mechanics analysis were used to assess functional residual capacity (FRC) and airway function. Moment analysis and lung clearance index were calculated as measures of gas mixing efficiency in distal airways. Respiratory rate, tidal volume, minute ventilation and indices of inspiratory drive were determined together with heart rate, blood pressure and oxygenation. RESULTS: No significant CH-induced changes were found for gas mixing efficiency, FRC or lung mechanics. Minute ventilation decreased slightly, but significantly, while indices of inspiratory drive remained unchanged. Heart rate increased significantly, but mean arterial blood pressure was unaffected. CONCLUSION: Moderate CH sedation did not significantly affect airway function or FRC. Although indices of inspiratory drive were not affected, minute ventilation decreased slightly. These findings indicate that reliable results can be obtained from lung function testing when CH is used for sedation.

CPAP of 4 cm H(2)O Has no short-term benefit at term in infants with BPD.

BACKGROUND: Lung development and function is compromised at term in infants with bronchopulmonary dysplasia (BPD), characterized by reduced functional residual capacity (FRC) and impaired gas-mixing efficiency in distal airways. OBJECTIVE: To determine whether continuous positive airway pressure (CPAP) improves FRC, ventilation, distal airway function, and gas exchange in spontaneously breathing infants with BPD. DESIGN/METHODS: Twenty-one infants with BPD (median birth weight 0.72 kg (range 0.50-1.27) and median gestational age 26 weeks (range 23-28)) were studied before and after CPAP of 4 cm H(2)O was applied by a facemask system. A multiple-breath nitrogen washout method was used to assess FRC, ventilation, and gas-mixing efficiency. Moment analysis and lung clearance index was calculated from the nitrogen-decay curve for assessment of gas-mixing efficiency. Transcutaneous (Tc) PO(2)/PCO(2) was monitored during stable infant conditions before each washout test. RESULTS: When CPAP was raised from 0 to 4 cm H(2)O, FRC increased significantly together with a significant increase in moment ratios (M(1)/M(0) and M(2)/M(0)). Tc PO(2) decreased significantly and the breathing pattern changed, with significantly reduced respiratory rate, minute ventilation, and alveolar ventilation. There was also an increase in tidal volume and dead space. CONCLUSIONS: CPAP of 4 cm H(2)O applied with a facemask at term to infants with BPD did not improve ventilation, gas-mixing efficiency in distal airways, or oxygenation despite an increase in FRC. We speculate that instead of promoting recruitment of unventilated lung volumes, increasing the end-expiratory pressure in infants with BPD may lead to an overexpansion of already ventilated parts of the lung, causing further compromise of lung function.

Abdominal pathology requiring laparotomy in very preterm infants is associated with need for surgical closure of patent ductus arteriosus.

BACKGROUND: Extensive intestinal surgery in very preterm infants and its influence on somatic growth is of major concern. There is little consensus as to which is the most appropriate surgical approach in extremely low-birth-weight infants with abdominal pathology. Laparotomy is currently advocated, but peritoneal drainage is also discussed. OBJECTIVE: To study laparotomy as surgical intervention in newborn infants with less than 28 gestational weeks and to investigate associated mortality and morbidity and its impact on short-term growth. STUDY DESIGN/METHODS: The study was a retrospective case-control study of newborn infants requiring laparotomy. All infants with gestational age less than 28 weeks who were subject to acute laparotomy in the neonatal period at Sahlgrenska University Hospital during a 5-year period (2003-2007) were included in the study (n = 20). The control group consisted of infants admitted to the unit with the same gestational age but not requiring laparotomy. Infants with severe malformations were excluded. SUMMARY AND CONCLUSION: Extensive abdominal surgery was feasible in very preterm infants. Necrotizing enterocolitis dominated the abdominal pathology requiring surgery. Patent ductus arteriosus requiring surgical closure occurred more often in the lapatotomy group and in those diagnosed as necrotizing enterocolitis. There was no impact on first year somatic growth.

Fetal nicotine exposure increases airway responsiveness and alters airway wall composition in young lambs.

To test the hypotheses that fetal nicotine exposure alters airway wall composition and enhances the airway response to inhaled methacholine (MCh), lambs were exposed during the last fetal trimester to (1) a low dose (LN) (n=13, 0.5mg/kg/d (maternal weight) of free base nicotine, (2) a moderate dose (MN) (n=10, 1.5mg/kg/d) or (3) saline (n=14). Studies were performed at postnatal days 12, 26 and 52. Prenatal nicotine exposure induced a dose- and age-related hyper-responsiveness to MCh in the proximal airways. Moment analysis of nitrogen decay curves showed no nicotine or MCh effects on ventilation homogeneity or gas-mixing efficiency in the distal airways during MCh inhalations suggesting a bimodal response. Fetal nicotine exposure increased epithelial mucosubstance volume in central (LN, MN) and distal bronchi (LN), increased smooth muscle volume in distal bronchi and bronchioles (LN) and decreased bronchiolar diameter (MN). In conclusion, third trimester nicotine exposure causes hyperreactive proximal airways and alters proximal airway wall composition associated with airflow limitation.

Effect of antenatal corticosteroid treatment on lung function in full-term newborn infants.

BACKGROUND: Antenatal treatment of pregnant women with corticosteroids in order to stimulate surfactant production has been shown to be effective. However, lung structure is also affected by the treatment. OBJECTIVE: We tested the hypothesis that changes within lung acini, induced by maternal corticosteroid treatment, persist during lung development. METHODS: Twenty-two healthy infants, whose mothers were treated with up to three doses of betamethasone at 25-33 weeks of pregnancy because of preterm labour, but where labour terminated and the infants were born at term, were studied at term and compared to a group of 50 healthy newborn infants without prenatal treatment with corticosteroids. Gas-mixing efficiency was measured in terms of moment ratio with a nitrogen washout method together with functional residual capacity. Mechanical parameters were assessed with the single occlusion technique. RESULTS: There were no signs of disturbed gas mixing or changed lung volume or mechanics in the treated group. CONCLUSION: The result contributes to an emerging body of evidence that antenatal treatment with corticosteroids does not permanently affect lung structure or function.

Transcutaneous blood gas monitoring during neonatal intensive care.

AIM: To evaluate the accuracy in transcutaneous (Tc) blood gas monitoring in newborn infants, including extremely low birth weight infants, during neonatal intensive care. METHODS: Tc PO(2) /PCO(2) was monitored in the neonatal intensive care unit (NICU) during stable infant conditions. In comparison, simultaneous arterial PO(2) and PCO(2) was measured. Sixty measurements were taken in 46 infants with median (range) birth weight of 0.93 (0.53-4.7) kg and at median (range) age of 8.5 (1-44) days. Comparison of measurements was performed using Bland-Altman plots, and the mean (95% CI) of the difference was calculated. Comparison was also performed in relation to body weight, postnatal age and oxygen requirement. RESULTS: The mean (95% CI) difference in PO(2) (TcPO(2)-aPO(2)) was 0.3 (-0.2-0.9) kPa, and the corresponding difference in PCO(2) (TcPCO(2)-aPCO(2)) was 0.4 (0.03-0.8, p < 0.05) kPa. Some differences were related to body weight, age and oxygen requirement, but these differences were small. CONCLUSION: There was good agreement between TcPO(2)/TcPCO(2) and corresponding arterial measurements. The mean difference between the methods was small and clinically acceptable in a current NICU. Tc blood gas monitoring could be recommended as a valuable complement for blood gas monitoring also in extremely low birth weight infants.

Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in 39,821 newborns.

OBJECTIVE: To evaluate the use of pulse oximetry to screen for early detection of life threatening congenital heart disease. DESIGN: Prospective screening study with a new generation pulse oximeter before discharge from well baby nurseries in West Götaland. Cohort study comparing the detection rate of duct dependent circulation in West Götaland with that in other regions not using pulse oximetry screening. Deaths at home with undetected duct dependent circulation were included. SETTING: All 5 maternity units in West Götaland and the supraregional referral centre for neonatal cardiac surgery. PARTICIPANTS: 39,821 screened babies born between 1 July 2004 and 31 March 2007. Total duct dependent circulation cohorts: West Götaland n=60, other referring regions n=100. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and likelihood ratio for pulse oximetry screening and for neonatal physical examination alone. RESULTS: In West Götaland 29 babies in well baby nurseries had duct dependent circulation undetected before neonatal discharge examination. In 13 cases, pulse oximetry showed oxygen saturations

Extreme preterm birth: onset of delivery and its effect on infant survival and morbidity.

OBJECTIVE: To investigate whether correlations could be found between the onset of preterm delivery and infant outcome, that is, survival and major morbidity. METHODS: The study was a retrospective, hospital-based cohort study. All women with a live fetus on admission, giving birth at 22(+0) to 27(+6) weeks of gestation between 1998 and 2003 were included. The deliveries were subdivided into those that began with either preterm labor, preterm premature rupture of membranes (PROM), or iatrogenic preterm delivery. These groups were compared for survival and survival without major morbidity (intraventricular hemorrhage grade 3-4, periventricular leukomalacia, retinopathy of prematurity grade 3-4, bronchopulmonary dysplasia, or necrotizing enterocolitis) at discharge. RESULTS: The cause of the preterm birth was preterm labor in 154 of 288 (53%), preterm PROM 83 of 288 (29%), and iatrogenic preterm delivery 51 of 288 (18%). There were 83% liveborn children, and 67% survived until discharge. Survival was lower for preterm PROM (54%) than for preterm labor (75%) and iatrogenic preterm delivery (67%). Multivariable analyses showed that survival was positively associated with gestational age and antenatal steroid treatment. Negative associations concerning survival were found for preterm PROM and being small for gestational age. Survival without major morbidity did not differ significantly between the groups and was positively associated with gestational age and negatively associated with being small for gestational age. CONCLUSION: Infant survival was significantly lower when the onset of preterm delivery was preterm PROM as compared with preterm labor and iatrogenic delivery. For surviving infants there was no significant difference in major morbidity between the groups. LEVEL OF EVIDENCE: III.

Prenatal nicotine exposure transiently alters the lung mechanical response to hypoxia in young lambs.

To test the hypothesis that fetal nicotine exposure alters the lung mechanical response to hypoxia (10% O(2)) 10 lambs were exposed during the last fetal trimester to a low dose nicotine (LN) and 10 to a moderate dose (MN) (maternal dose 0.5 and 1.5mg/(kgday) free base, respectively). There were 10 controls (C). At 12 days, minute ventilation increased significantly less in MN compared with LN but not with C. In contrast to C and LN, MN did not show anticipated increases in dynamic compliance, specific compliance and FRC or decrease in lung resistance but had signs of airway hyperreactivity during hypoxia. Nicotine exposure did not alter the cardiovascular response. These adverse effects decreased with advancing age. In summary, prenatal nicotine exposure alters the lung mechanical response to hypoxia. We speculate that prenatal nicotine-induced alterations of lung mechanics during hypoxia may contribute to an increased vulnerability to hypoxic stress during infancy.

Direct measurement of airway pressure in ventilated very low birth weight infants.

A new method for direct measurement of airway pressure using a fiber optic pressure sensor (FOPS) has been tested in very low birth weight infants during mechanical ventilation. Airway pressure and ventilatory flow was recorded in an initial investigation in three newborn infants with a birth weight less than 1000 g. The method for direct measurement of airway pressure was found to be feasible in ventilated infants and can form a basis for reliable measurements which can be used to derive information on lung function and to guide in finding an effective ventilator management.

Screening for duct-dependant congenital heart disease with pulse oximetry: a critical evaluation of strategies to maximize sensitivity.

AIM: To evaluate the feasibility of detecting duct-dependent congenital heart disease before hospital discharge by using pulse oximetry. DESIGN: Case-control study. SETTING: A supra-regional referral centre for paediatric cardiac surgery in Sweden. PATIENTS: 200 normal term newborns with echocardiographically normal hearts (median age 1.0 d) and 66 infants with critical congenital heart disease (CCHD; median age 3 d). METHODS: Pulse oximetry was performed in the right hand and one foot using a new-generation pulse oximeter (NGoxi) and a conventional-technology oximeter (CToxi). RESULTS: With the NGoxi, normal newborns showed a median postductal saturation of 99% (range 94-100%); intra-observer variability showed a mean difference of 0% (SD 1.3%), and inter-observer variability was 0% (SD 1.5%). The CToxi recorded a significantly greater proportion of postductal values below 95% (41% vs 1%) in the normal newborns compared with NGoxi (p<0.0001). The CCHD group showed a median postductal saturation of 90% (45-99%) with the NGoxi. Analysis of distributions suggested a screening cut-off of <95%; however, this still gave 7/66 false-negative patients, all with aortic arch obstruction. Best sensitivity was obtained by adding one further criterion: saturation of <95% in both hand and foot or a difference of >+/-3% between hand and foot. These combined criteria gave a sensitivity of 98.5%, specificity of 96.0%, positive predictive value of 89.0% and negative predictive value of 99.5%. CONCLUSION: Systematic screening for CCHD with high accuracy requires a new-generation oximeter, and comparison of saturation values from the right hand and one foot substantially improves the detection of CCHD.

Cardiorespiratory effects of nicotine exposure during development.

Exposure to tobacco smoke is a major risk factor for the sudden infant death syndrome. Nicotine is thought to be the ingredient in tobacco smoke that is responsible for a multitude of cardiorespiratory effects during development, and pre- rather than postnatal exposure is considered to be most detrimental. Nicotine interacts with endogenous acetylcholine receptors in the brain and lung, and developmental exposure produces structural changes as well as alterations in neuroregulation. Abnormalities have been described in sympathicovagal balance, arousal threshold and latency, breathing pattern at rest and apnea frequency, ventilatory response to hyperoxia or hypoxia, heart rate regulation and ability to autoresuscitate during severe hypoxia. This review discusses studies performed on infants of smoking mothers and nicotine-exposed animals yielding varying and sometimes inconsistent results that may be due to differences in experimental design, species and the dose of exposure. Taken together however, developmental nicotine exposure appears to induce vulnerability during hypoxia and a potential inability to survive severe asphyxia.

Lung function at term reflects severity of bronchopulmonary dysplasia.

OBJECTIVE: To test whether infants with bronchopulmonary dysplasia (BPD) express the same functional impairments at term as healthy, preterm infants, and whether clinical severity of BPD is qualitatively or quantitatively related. STUDY DESIGN: Prospective measurements on a consecutive sample of 50 infants with BPD and 19 healthy preterm controls in a university hospital. BPD infants were classified as "severe," "moderate," or "mild," according to their need for oxygen. A multiple-breath nitrogen wash-out method was used to assess functional residual capacity (FRC) and gas mixing efficiency. Mechanical variables were estimated by the occlusion test. RESULTS: Infants with severe BPD had lower FRC, less efficient gas mixing, and higher specific conductance than those with mild and moderate BPD, and the preterm controls. Mild and moderate BPD did not differ in any property from each other but differed from controls in the same variables. The elastic properties of the respiratory system appeared unaffected by BPD. CONCLUSIONS: The ventilatory impairments in BPD were of the same nature as in healthy preterm infants when compared with term infants, but their magnitude was related to the clinical severity of the BPD. Gas mixing efficiency together with FRC appears to be useful to assess lung development in BPD.

[Unexpected out-of-hospital deliveries--experiences from the Gothenburg area. Centralized obstetrical care requires competent ambulance staff]. / Oväntad förlossning utanför sjukhus--erfarenheter från Göteborgsregionen. Centraliserad förlossningsvård kräver kompetent ambulanspersonal.

One hundred and sixty-seven women gave birth before arrival at the hospital during a six-year period in the Göteborg area. Most of these women had given birth before. The actual delivery most often started at term during the night, proceeded normally but rapidly and the neonatal outcome was good. Sixty-two per cent of the women delivered at home. Complicated lacerations or major hemorrhages were uncommon. The distance to the delivery ward was one of the risk factors for prehospital delivery. This is important to take into consideration in the ongoing process of centralizing the delivery clinics. Basic knowledge in obstetrics is mandatory for the ambulance personnel, as well as regular observation visits to the delivery ward and practice in birth simulators.

N-acetylcysteine administration during the first week of life does not improve lung function in extremely low birth weight infants.

Oxygen toxicity is thought to be an important factor involved in development of bronchopulmonary dysplasia (BPD) in the very preterm infant. Glutathione (GSH) plays a major role in the antioxidant defense system in the preterm lung and there are theoretical implications that N-acetylcysteine (NAC) treatment could improve its function. The purpose of this study was to investigate whether NAC treatment during the first week of life to preterm infants improved neonatal lung function as a measure of lung injury. The study was part of a multi-center Nordic controlled trial with prophylactic intravenous NAC treatment (16-32 mg/kg/day) for 6 days in newborn infants with birth weights 500-999 g. Lung mechanics, with calculations of compliance and resistance of the respiratory system, together with measurements of functional residual capacity and indices of gas mixing efficiency in the lung, were performed in 33 preterm infants (18 received NAC and 15 placebo) before discharge from the NICU. Median (range) gestational age was 25 (24-28) weeks in the NAC-treated infants and 25 (24-29) in the placebo group. Corresponding mean (SD) birth weights were 0.774 (0.11) and 0.761 (0.12) kg respectively. Lung function measurements did not show any significant differences between NAC-treated infants compared to placebo when examined before discharge from the NICU. We conclude that prophylactic NAC treatment to extremely low birth weight infants during the first week of life does not improve lung function at term.

Altered lung development after prenatal nicotine exposure in young lambs.

There is compelling evidence that prenatal nicotine exposure permanently alters lung development and airway function. The aim of this study was to determine how prenatal nicotine exposure alters proximal and distal airway function. Thirteen lambs were continuously exposed during the last fetal trimester to low-dose nicotine (LN) and 12 to a moderate dose (MN) (maternal s.c. dose: 0.5 and 1.5 mg/kg/d, respectively). Ten lambs served as controls (C). Proximal airway function was measured by lung mechanics. A multiple-breath N2 washout technique was used to measure lung volume (functional residual capacity) and efficiency of gas mixing in distal airways, i.e. terminal respiratory units (moment ratio and nitrogen clearance). In comparison with C, both LN and MN had significantly reduced specific airway conductance to the same extent at a median study age of 12, 25, and 51 d, indicating signs of proximal airway obstruction. Distal airway function showed significant improvement in LN. Ventilation and functional residual capacity were unaffected. In summary, prenatal nicotine exposure induced airway obstruction in proximal airways and improved gas mixing in distal airways, possibly reflecting restriction in proximal airway growth and accelerated maturation of the acinar part of the lung, respectively. We speculate that prenatal nicotine exposure has a disparate impact on airway development and function. The effect on the distal airways seemed to be inversely related to dose, which was not the case in the large airways. The altered airway function persisted during the study period, indicating that the effects of prenatal nicotine exposure might be permanent.