Presurgical pulmonary function tests in the first few days of life in neonates with congenital heart disease, a pilot study.

OBJECTIVE: To compare early pulmonary function tests (PFTs) in neonates with critical congenital heart disease (CHD) compared to a historical reference group. DESIGN: Infants ≥ 37 weeks gestation with critical CHD were studied within the first few days of life, prior to cardiac surgery, and compared to data from a published reference group of healthy term neonates without CHD, studied at the same institution. Passive respiratory resistance (Rrs) and compliance (Crs) were measured with the single breath occlusion technique following specific acceptance criteria. The study was powered for a 30% difference in Rrs. RESULTS: PFTs in 24 infants with CHD were compared to 31 historical reference infants. There was no difference in the Rrs between the groups. The infants with CHD had a significantly decreased Crs (1.02 ± 0.26 mL/cmH2O/kg versus 1.32 ± 0.36; (p < 0.05; mean ± SD)). CONCLUSIONS: Further prospective studies are required to quantify early PFTs in infants with CHD of different phenotypes.

Presurgical Pulmonary Function Tests in the First Few Days of Life in Neonates with Congenital Heart Disease, A Pilot Study.

Objective: To compare early pulmonary function tests (PFTs) in neonates with critical congenital heart disease (CHD) compared to a historical reference group. Design: Infants > 37 weeks gestation with critical CHD were studied within the first few days of life and prior to cardiac surgery and compared to data from a published reference group. Passive respiratory resistance (Rrs) and compliance (Crs) were measured with the single breath occlusion technique following specific acceptance criteria. The study was powered for a 30% difference in Rrs. Results: PFTs in 24 infants with CHD were compared to 31 historical reference infants. There was no difference in the Rrs between the groups. The infants with CHD had a significantly decreased Crs (1.02 ± 0.26 mL/cmH2O/kg versus 1.32 ± 0.36; (p < 0.05; mean ± SD)). Conclusions: Further prospective studies are required to quantify early PFTs in infants with CHD of different phenotypes.

Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years: Follow-up of a Randomized Clinical Trial.

Importance: Vitamin C supplementation (500 mg/d) for pregnant smokers has been reported to increase offspring airway function as measured by forced expiratory flow (FEF) through age 12 months; however, its effects on airway function at age 5 years remain to be assessed. Objective: To assess whether vitamin C supplementation in pregnant smokers is associated with increased and/or improved airway function in their offspring at age 5 years and whether vitamin C decreases the occurrence of wheeze. Design, Setting, and Participants: This study followed up the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) double-blind, placebo-controlled randomized clinical trial conducted at 3 centers in the US (in Oregon, Washington, and Indiana) between 2012 and 2016. Investigators and participants remain unaware of the treatment assignments. Forced expiratory flow measurements at age 5 years were completed from 2018 to 2021. Interventions: Pregnant smokers were randomized to vitamin C (500 mg/d) or placebo treatment. Main Outcomes and Measures: The primary outcome was the prespecified measurement of FEF between 25% and 75% expired volume (FEF25-75) by spirometry at age 5 years. Secondary outcomes included FEF measurements at 50% and 75% of expiration (FEF50 and FEF75), forced expiratory volume in 1 second (FEV1), and occurrence of wheeze. Results: Of the 251 pregnant smokers included in this study, 125 (49.8%) were randomized to vitamin C and 126 (50.2%) were randomized to placebo. Of 213 children from the VCSIP trial who were reconsented into this follow-up study, 192 (90.1%) had successful FEF measurements at age 5 years; 212 (99.5%) were included in the analysis of wheeze. Analysis of covariance demonstrated that offspring of pregnant smokers allocated to vitamin C compared with placebo had 17.2% significantly higher mean (SE) measurements of FEF25-75 at age 5 years (1.45 [0.04] vs 1.24 [0.04] L/s; adjusted mean difference, 0.21 [95% CI, 0.13-0.30]; P < .001). Mean (SE) measurements were also significantly increased by 14.1% for FEF50 (1.59 [0.04] vs 1.39 [0.04] L/s; adjusted mean difference, 0.20 [95% CI, 0.11-0.30]; P < .001), 25.9% for FEF75 (0.79 [0.02] vs 0.63 [0.02] L/s; 0.16 [95% CI, 0.11-0.22]; P < .001), and 4.4% for FEV1 (1.13 [0.02] vs 1.09 [0.02] L; 0.05 [95% CI, 0.01-0.09]; P = .02). In addition, offspring of pregnant smokers randomized to vitamin C had significantly decreased wheeze (28.3% vs 47.2%; estimated odds ratio, 0.41 [95% CI, 0.23-0.74]; P = .003). Conclusions and Relevance: In this follow-up study of offspring of pregnant smokers randomized to vitamin C vs placebo, vitamin C supplementation during pregnancy resulted in significantly increased airway function of offspring at age 5 years and significantly decreased the occurrence of wheeze. These findings suggest that vitamin C supplementation for pregnant smokers may decrease the effects of smoking in pregnancy on childhood airway function and respiratory health. Trial Registration: ClinicalTrials.gov Identifier: NCT03203603.

Premature monochorionic monoamniotic twins have lower lung compliance at birth than matched dichorionic diamniotic twins.

BACKGROUND: Premature infants are born with immature lungs that demonstrate abnormal pulmonary function with differences in passive respiratory system compliance and resistance, and functional residual capacity. To our knowledge, no studies have evaluated differences in neonatal pulmonary function based on the type of twin gestation, or chorionicity. Given the effect of chorionicity on outcomes, we aimed to study the effect of twin type, monochorionic monoamniotic (MCMA) vs dichorionic diamniotic (DCDA), on neonatal early pulmonary function tests. METHODS: In this prospective cohort study, 5 sets of DCDA twins were matched to 5 sets of MCMA twins on gestational age at delivery, latency from antenatal corticosteroid exposure, birthweight, race and gender. Mean values were compared for passive respiratory system compliance and resistance, functional residual capacity, and tidal volume. RESULTS: MCMA infants had a significantly lower compliance (0.64 vs 1.25 mL/cm H2O /kg; p = 0.0001) and significantly higher resistance (0.130 vs 0.087 cm H2O /mL/sec; p = 0.0003) than DCDA infants. Functional residual capacity was lower for MCMA than DCDA infants (17.5 vs 23.4 mL/kg; p = 0.17). Further, 80% of MCMA infants required intubation for surfactant administration compared to 20% of DCDA infants, indicating the clinical significance of these objective measures. CONCLUSIONS: Due to the matched case-control design, causality cannot be established. However, we speculate that these differences in lung function may derive from differential exposure to preterm labor and endogenous maternal corticosteroid exposure. Further study is necessary to establish the true causal relationship.

Perioperative Improvement in Pulmonary Function in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: The objective of this study was to compare serial changes in pulmonary function in contemporary infants with congenital diaphragmatic hernia managed with a gentle ventilation approach. STUDY DESIGN: Observational cohort, single-center study of infants ≥350/7 weeks gestation at delivery with congenital diaphragmatic hernia. Functional residual capacity (FRC), passive respiratory compliance, and passive respiratory resistance were measured presurgical and postsurgical repair and within 2 weeks of discharge. A 1-way analysis of variance for repeated measures was used to evaluate the change in FRC, passive respiratory compliance, and passive respiratory resistance over these repeated measures. RESULTS: Twenty-eight infants were included in the analysis with a mean gestational age of 38.3 weeks and birth weight of 3139 g. We found a significant increase in FRC across the 3 time points (mean in mL/kg [SD]: 10.9 [3.6] to 18.5 [5.2] to 24.2 [4.4]; P < .0001). There was also a significant increase in passive respiratory compliance and decrease in passive respiratory resistance. In contrast to a previous report, there were survivors in the current cohort with a preoperative FRC of <9 mL/kg. The mean FRC measured at discharge was in the range considered within normal limits. Sixteen infants had prenatal measurements of the lung-to-head ratio, but there was no relationship between the lung-to-head ratio and preoperative or postoperative FRC measurements. CONCLUSIONS: Infants with congenital diaphragmatic hernia demonstrate significant increases in FRC and improvements in respiratory mechanics measured preoperatively and postoperatively and at discharge. We speculate these improvements are due to the surgical resolution of the mechanical obstruction to lung recruitment and that after achieving preoperative stability, repair should not be delayed given these demonstrable postoperative improvements.

Pulmonary Function Tests in Very Low Birth Weight Infants Screened for Pulmonary Hypertension: A Pilot Study.

OBJECTIVE: To compare pulmonary function tests (PFTs), specifically respiratory system resistance (Rrs) and compliance (Crs), in very low birth weight (VLBW) infants with and without pulmonary hypertension. STUDY DESIGN: Infants were included who underwent PFTs at 34-38 weeks postmenstrual age (PMA) as part of our pulmonary hypertension screening guidelines for infants born at ≤1500 g requiring respiratory support at ≥34 weeks PMA. One pediatric cardiologist reviewed and estimated right ventricular or pulmonary arterial pressure and defined pulmonary hypertension as an estimated pulmonary arterial pressure or right ventricular pressure greater than one-half the systemic pressure. Rrs and Crs were measured with the single breath occlusion technique and functional residual capacity with the nitrogen washout method according to standardized criteria. RESULTS: Twelve VLBW infants with pulmonary hypertension and 39 without pulmonary hypertension were studied. Those with pulmonary hypertension had significantly lower birth weight and a trend toward a lower gestational age. There were no other demographic differences between the groups. The infants with pulmonary hypertension had significantly higher Rrs (119 vs 78 cmH2O/L/s; adjusted P = .012) and significantly lower Crs/kg (0.71 vs 0.92 mL/cmH2O/kg; P = .04). CONCLUSIONS: In this pilot study of VLBW infants screened for pulmonary hypertension at 34-38 weeks PMA, those with pulmonary hypertension had significantly increased Rrs and decreased Crs compared with those without pulmonary hypertension. Additional studies are needed to further phenotype infants with evolving BPD and pulmonary hypertension.

Hair and nail nicotine levels of mothers and their infants as valid biomarkers of exposure to intrauterine tobacco smoke.

INTRODUCTION: Tobacco use remains the single most modifiable cause of adverse pregnancy outcomes. It is crucial to be able to accurately quantify the burden of tobacco exposure on both the mother and fetus to have better measures of efficacy with interventions being studied. METHODS: This is a descriptive and exploratory study conducted within a randomized controlled trial. Pregnant smoking and non-smoking women were followed from ≤22 weeks' gestation through delivery with monthly maternal smoking questionnaires, urine cotinine levels, and collection of maternal and infant hair and nail samples, at delivery. Nicotine was extracted and measured (ng/mg) using high-performance liquid chromatography with electrochemical detection. RESULTS: Forty-six mother-infant dyads (34 pregnant smokers and 12 pregnant non-smokers) had successful completion of maternal and infant hair and nails samples. The median hair nicotine levels of the smoking mothers and their infants was significantly higher than those of the non-smokers (1.015 vs 0.037 ng/ mg, p<0.05 for the mothers; 0.445 vs 0.080 ng/mg, p<0.01 for the infants). Similarly, the median nail nicotine levels for smoking mothers and their infants were significantly higher than the non-smokers (2.130 vs 0.056 ng/mg, p<0.01 for the mothers; 0.594 vs 0.132 ng/mg, p<0.05 for the infants). We found a moderate but significant correlation between maternal hair and nail nicotine (r=0.64, p<0.001), infant hair and nail nicotine (r=0.64; p<0.001), maternal and infant hair nicotine (r=0.61, p<0.001), and maternal and infant nail nicotine levels (r=0.58, p<0.001). CONCLUSIONS: Our study shows that both infant hair and nail nicotine levels are valid biomarkers of intrauterine tobacco smoke exposure, and can be used to identify prenatal smoke exposure, correlating well with the level of maternal nicotine exposure.

Pulmonary function in extremely low birth weight infants with bronchopulmonary dysplasia before hospital discharge.

OBJECTIVE: To compare pulmonary function in extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) studied at 34-36 weeks postmenstrual age (PMA) with a reference group of "healthy" infants born at 34-36 weeks. We hypothesized that ELBW infants have decreased functional residual capacity (FRC) and respiratory compliance (Crs). STUDY DESIGN: Pulmonary function testing was performed at 34-36 weeks PMA in infants with BPD and within 96 h of age in infants delivered at 34-36 weeks. RESULTS: Twenty BPD patients and 20 healthy infants were studied. FRC (18.9 versus 26.2 mL/kg; adjusted 95% CI 5.0, 10.9; P < 0.001) and Crs (0.80 versus 1.29-mL/cm H2O/kg; 95% CI 0.31, 0.71; P < 0.001) were decreased in BPD patients. Respiratory resistance was increased in BPD patients. CONCLUSIONS: ELBW infants with BPD have decreased pulmonary function compared to healthy infants delivered at 34-36 weeks. This suggests that infants with BPD have smaller lung volumes.

Vitamin C to Pregnant Smokers Persistently Improves Infant Airway Function to 12†Months of Age: A Randomised Trial.

BACKGROUND: Vitamin C (500 mg·day-1) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3 months of age. Its effect on airway function through 12 months of age has not been reported. OBJECTIVE: To assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age. METHODS: This is a prespecified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23 weeks of gestation: 125 to 500 mg·day-1 vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12 months of age were analysed by repeated measures analysis of covariance. RESULTS: FEFs were performed in 222 infants at 3 months and 202 infants at 12 months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were: 40.2 mL·sec-1 for FEF75 (adjusted 95% CI for difference 6.6 to 73.8; p=0.025); 58.3 mL·sec-1 for FEF50 (95% CI 10.9 to 105.8; p=0.0081); and 55.1 mL·sec-1 for FEF25-75 (95% CI, 9.7 to 100.5; p=0.013). CONCLUSIONS: In offspring of pregnant smokers randomised to vitamin C versus placebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12 months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway.

The Effect of Extended Continuous Positive Airway Pressure on Changes in Lung Volumes in Stable Premature Infants: A Randomized Controlled Trial.

OBJECTIVE: To compare changes in lung volumes, as measured by functional residual capacity (FRC), through to discharge in stable infants randomized to 2 weeks of extended continuous positive airway pressure CPAP (eCPAP) vs CPAP discontinuation (dCPAP). STUDY DESIGN: Infants born at ≤32 weeks of gestation requiring ≥24 hours of CPAP were randomized to 2 weeks of eCPAP vs dCPAP when meeting CPAP stability criteria. FRC was measured with the nitrogen washout technique. Infants were stratified by gestational age (<28 and ≥ 28 weeks) and twin gestation. A linear mixed-effects model was used to evaluate the change in FRC between the 2 groups. Data were analyzed blinded to treatment group allocation. RESULTS: Fifty infants were randomized with 6 excluded, for a total of 44 infants. Baseline characteristics were similar in the 2 groups. The infants randomized to eCPAP vs dCPAP had a greater increase in FRC from randomization through 2 weeks (12.6 mL vs 6.4 mL; adjusted 95% CI, 0.78-13.47; P = .03) and from randomization through discharge (27.2 mL vs 17.1 mL; adjusted 95% CI, 2.61-17.59; P = .01). CONCLUSIONS: Premature infants randomized to eCPAP had a significantly greater increase in FRC through discharge compared with those randomized to dCPAP. An increased change in FRC may lead to improved respiratory health. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02249143.

Pulmonary Function and Systolic Blood Pressure in Very Low Birth Weight Infants at 34 - 36 Weeks of Corrected Age.

PURPOSE: Preterm infants are at increased risk of systemic hypertension compared to term infants. Bronchopulmonary dysplasia (BPD) has been shown to be associated with hypertension in preterm infants albeit with no causation reported. BPD is characterized by abnormal pulmonary function tests (PFTs), specifically elevated passive respiratory resistance (Rrs), decreased passive respiratory compliance (Crs) and decreased functional residual capacity (FRC). There have been no studies comparing PFTs in very low birth weight (VLBW) infants with and without hypertension. We hypothesized that stable VLBW infants with hypertension will have altered PFTs. PATIENTS AND METHODS: Retrospective cohort study of infants < 1500 grams at birth (VLBW) who had PFTs performed near 34-36 weeks of corrected gestational age (CGA). We excluded infants with congenital anomalies, known hypertensive disorders or those at risk of medication-induced hypertension. Data obtained included PFT parameters (Rrs, Crs, FRC) and mean systolic blood pressure (SBP). RESULTS: 59 VLBW infants were identified for analysis, 14 with and 45 without hypertension. Hypertensive and normotensive patients were similar in terms of mean gestational age (26.6 vs 27.4 weeks), mean CGA at PFTs (36.1 vs 34.6 weeks) and proportion of BPD (36% vs 36%). The Rrs was significantly higher in hypertensive versus normotensive patients [median Rrs of 0.080 (0.069, 0.090) versus 0.066 (0.054, 0.083) cmH2O/mL/sec; p = 0.04]. There was no difference in systolic blood pressure in the infants with and without BPD. CONCLUSION: In this cohort of contemporary VLBW infants, those with hypertension had increased Rrs. This finding warrants a prospective study with a larger sample size and long-term follow-up.

Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial.

Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF50 and FEF25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, -3.33 to 35.64; P = 0.10), FEF50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF50 and FEF25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF50 and FEF25-75) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).

Respiratory Compliance in Late Preterm Infants (340/7-346/7 Weeks) after Antenatal Steroid Therapy.

OBJECTIVE: To compare respiratory compliance in late preterm infants (340/7-346/7 weeks) who received antenatal steroids vs matched late preterm infants who did not receive antenatal steroids. STUDY DESIGN: This was a single-center prospective cohort study. Patients were matched for birth weight, gestational age, race, and sex. Respiratory compliance was the primary outcome measured with the single breath occlusion technique. RESULTS: We studied 25 late preterm infants treated with antenatal steroids and 25 matched infants who did not receive antenatal steroids. The treated infants had a significantly increased respiratory compliance/kg (adjusted 95% CI 0.05, 0.49; P = .016) and fewer required continuous positive airway pressure (P = .007) or >24 hours of supplemental oxygen (P = .046). There was no difference in surfactant therapy. CONCLUSIONS: Respiratory compliance was significantly increased in this cohort of late preterm infants born at 340/7-346/7 weeks who received antenatal steroids compared with matched infants who did not receive antenatal steroids. Although not randomized, these data provide physiologic support for the possible beneficial effects of antenatal steroids in late preterm infants.

The window of improved neonatal respiratory compliance after rescue antenatal steroids.

OBJECTIVE: To evaluate whether premature infants delivered ≤7 days after rescue antenatal steroid treatment (ideal treatment) have increased passive respiratory compliance compared to those delivered >7 days after treatment (remote treatment). METHODS: Secondary analysis of a randomized trial of rescue antenatal steroids on respiratory compliance. Infants in the treatment group were stratified by the interval between rescue antenatal steroids and delivery. We then compared the respiratory compliance in the ideal vs. remote groups. RESULTS: Forty-four women (56 infants) received rescue antenatal steroids. Forty-nine infants had evaluable respiratory compliance measurements, with 27 (GA 30.1 weeks, BW 1362 g) "ideally" treated, and 22 (GA 33.8 weeks, BW 2248 g) "remotely" treated. Respiratory compliance was significantly higher for the ideal compared to the remote group (1.32 vs. 1.06 mL/cm H2O/kg; p = 0.037). CONCLUSION: Infants treated with rescue antenatal steroids have a significantly higher respiratory compliance if delivery occurs within 7 days after treatment.

Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP): Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health.

Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in >450,000 smoke-exposed infants born yearly. Smoking during pregnancy is the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to evaluate pulmonary function at 3months of age in infants delivered to pregnant smokers randomized to 500mg/day of vitamin C versus placebo during pregnancy. Secondary aims evaluate the incidence of wheezing through 12months and pulmonary function testing at 12months of age. Women are randomized between 13 and 23weeks gestation from clinical sites in Portland, Oregon at Oregon Health & Science University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from randomization to delivery. Monthly contact with participants and monitoring of medical records is performed to document medication adherence, changes in smoking and medical history, and adverse events. Pulmonary function testing of offspring occurs at 3 and 12months of age and incidence of wheezing and respiratory illness through 12months is captured via at least quarterly questionnaires. Ancillary studies are investigating the impact of vitamin C on placental blood flow and DNA methylation.

Pulmonary function and outcomes in infants randomized to a rescue course of antenatal steroids.

BACKGROUND/OBJECTIVE: Our objective was to obtain follow-up pulmonary function testing and assessment of clinical respiratory outcomes, at 1-2 years, in preterm infants whose mothers were randomized to a single rescue course of antenatal steroids (AS) versus placebo. METHODS: Follow-up of a randomized, double-blinded trial. In the original trial pregnant women ≥14 days after initial course of AS were randomized to rescue AS or placebo. Pulmonary function testing and a standardized respiratory questionnaire were obtained at 1-2 years of corrected age. Respiratory compliance (Crs) was measured with the single-breath occlusion and functional residual capacity (FRC) with the nitrogen washout method. Analysis was by intention-to-treat. RESULTS: A total of 96 (87%) of available survivors were administered a respiratory questionnaire. Seventy-seven percent of available patients had pulmonary function testing performed. There was no significant difference between groups in incidence of wheezing, asthma, respiratory syncytial virus infection, respiratory readmissions, use of bronchodilators or other medications, or in measurements of pulmonary function. There was also no significant difference in corrected age at study, race, gender, or length at the time of pulmonary function testing. Infants in the rescue group had a comparable mean FRC (249.4 mL vs 246.2 mL; adjusted 95%CI for difference -15.45, 38.20; P = 0.37) versus placebo. There were no differences in tidal volume or Crs. CONCLUSION: A rescue course of AS significantly increases Crs within 72 h of age and decreases oxygen need in newborn infants, without an adverse impact on pulmonary function or clinical respiratory outcomes at 1-2 years of age [NCT00669383].

Pulmonary Function at Hospital Discharge in Preterm Infants Randomized to a Single Rescue Course of Antenatal Steroids.

OBJECTIVE: To compare the pulmonary function, measured at birth and at hospital discharge, of infants whose mothers had been randomized to a single rescue course of antenatal steroids versus those whose mothers had been randomized to placebo. STUDY DESIGN: This study involved follow-up at hospital discharge of subjects of a randomized, double-blinded trial. In the original trial, pregnant women at ≥14 days after their initial course of antenatal steroids and <34 weeks' gestation were randomized to rescue antenatal steroids (44 mothers, 56 infants) or placebo (41 mothers, 57 infants). Passive respiratory compliance (Crs), passive respiratory resistance, and functional residual capacity were measured in all infants at birth and again at discharge to evaluate changes in pulmonary mechanics over time. Statistical analyses were based on intention to treat. RESULTS: We previously reported that compared with infants in the placebo group, infants in the rescue antenatal steroids group had a higher mean Crs value measured within 72 hours of birth (1.21 vs 1.01 mL/cm H2O/kg; P < .05). Here we show that the Crs benefit in the antenatal steroids group was sustained until discharge. Infants in the placebo group demonstrated improvement in Crs such that by discharge, there was no difference in mean Crs between the rescue antenatal steroids and placebo groups (1.18 vs 1.22 mL/cm H2O/kg). CONCLUSIONS: Rescue antenatal steroids significantly increased Crs measured within 72 hours of birth, and this increase was sustained until hospital discharge. Preterm infants in the placebo group demonstrated a decreased initial Crs compared with the rescue antenatal steroids group, but achieved a comparable Crs by the time of discharge. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669383.

Response to bronchodilators in very preterm infants with evolving bronchopulmonary dysplasia.

BACKGROUND: There are few effective and safe medications to treat very low birth weight (VLBW) infants with evolving BPD. Bronchodilators are often given to patients who have clinical signs of reactive airway disease, but there is not enough information regarding their effectiveness within this population. OBJECTIVE: To quantify the pulmonary function response to bronchodilator therapy in a population of VLBW infants with evolving BPD. DESIGN/METHODS: This is a retrospective analysis of an ongoing large database of pulmonary function tests (PFTs) in premature infants. We reviewed pre and post bronchodilator PFTs ordered by a physician due to concern for reactive airway disease. Inclusion criteria: BW< 1500 grams; > 14 days of age; admission diagnosis of respiratory distress syndrome; requiring ongoing oxygen, CPAP or ventilator support at the time of PFT. PFTs were done prior to albuterol therapy and repeated 30 minutes after the therapy was given. PFTs included the measurement of passive respiratory mechanics with the single breath occlusion technique, including passive respiratory compliance (Crs), resistance (Rrs) and tidal volume (Vt). RESULTS: 40 VLBW infants (mean gestation of 27.4 weeks; mean birth weight (BW) of 848 grams) were identified as having PFTs. 29 of these patients had a BW of ≤ 1000 grams. Patients were studied at a mean corrected gestational age of 34.9 weeks. 29 of 40 were extubated at the time of the PFT. Of these patients, 21 (52.5%) had a decrease in Rrs of ≥10%. From the other 19 patients, 5 (12.5%) had a decrease of 0 to < 10% in Rrs, 14 (35%) showed no response to therapy. There was no significant difference in Crs between groups.

Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.

IMPORTANCE: Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE: To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS: Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES: The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS: Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE: Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00632476.

Respiratory function in healthy late preterm infants delivered at 33-36 weeks of gestation.

OBJECTIVE: To compare pulmonary function testing including respiratory compliance (Crs) and time to peak tidal expiratory flow to expiratory time (TPTEF:TE) at term corrected age in healthy infants born at 33-36 weeks of gestation versus healthy infants delivered at term. STUDY DESIGN: We performed a prospective cohort study of late preterm infants born at 33-36 weeks without clinical respiratory disease (<12 hours of >0.21 fraction of inspired oxygen) and studied at term corrected age. The comparison group was term infants matched for race and sex to the preterm infants and studied within 72 hours of delivery. Crs was measured with the single breath occlusion technique. A minimum of 50 flow-volume loops were collected to estimate TPTEF:TE. RESULTS: Late preterm infants (n = 31; mean gestational age 34.1 weeks, birth weight 2150 g) and 31 term infants were studied at term corrected age. The late preterm infants had decreased Crs (1.14 vs 1.32 mL/cm H(2)O/kg; P < .02) and decreased TPTEF:TE (0.308 vs 0.423; P < .01) when compared with the term infants. Late preterm infants also had an increased respiratory resistance (0.064 vs 0.043 cm H(2)O/mL/s; P < .01). CONCLUSIONS: Healthy late preterm infants (33-36 weeks of gestation) studied at term corrected age have altered pulmonary function when compared with healthy term infants.