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].

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.

Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial.

OBJECTIVE: To compare respiratory compliance and functional residual capacity in infants randomized to a rescue course of antenatal steroids vs placebo. STUDY DESIGN: Randomized, double-blinded trial. Pregnant women > or =14 days after initial antenatal steroids were randomized to rescue antenatal steroids or placebo. The primary outcomes were measurements of respiratory compliance and functional residual capacity. This study is registered with clinicaltrials.gov (NCT00669383). RESULTS: Forty-four mothers (56 infants) received rescue antenatal steroids and 41 mothers (57 infants) received placebo. There was no significant difference in birthweight, or head circumference. Infants in the rescue group had an increased respiratory compliance (1.21 vs 1.01 mL/cm H(2)O/kg; adjusted 95% confidence interval, 0.01-0.49; P = .0433) compared with placebo. 13% in the rescue vs 29% in the placebo group required > or =30% oxygen (P < .05). Patients delivered at < or =34 weeks had greater pulmonary benefits. CONCLUSION: Infants randomized to rescue antenatal steroids have a significantly increased respiratory compliance compared with placebo.

Decreased respiratory compliance in infants less than or equal to 32 weeks' gestation, delivered more than 7 days after antenatal steroid therapy.

OBJECTIVES: Our objective was to compare the pulmonary function (respiratory compliance) of infants who were < or = 32 weeks' gestation and delivered > 7 days after a single course of antenatal steroids versus infants who were delivered 1 to 7 days after a single course of antenatal steroids. METHODS: A prospective cohort study of respiratory system compliance was conducted of infants < or = 32 weeks' gestation within 72 hours of life and before surfactant therapy if needed. The study (remote) group was composed of infants who were treated with antenatal steroids > 7 days before delivery and the comparison group (ideal group) of matched infants who were treated with antenatal steroids 1 to 7 days before delivery. Respiratory system compliance was measured with the single-breath occlusion technique. RESULTS: Twenty-eight remotely treated infants and 28 ideally treated infants were studied. The remote group had a significantly lower respiratory system compliance per kilogram and total respiratory system compliance when compared with the ideal antenatal steroids group. Within the remote group, infants who received antenatal steroids 8 to 14 days (n = 10) before delivery had a significantly higher respiratory system compliance and a trend to less surfactant need (10% vs 33%) as compared with infants who received antenatal steroids > 14 days (n = 18) before delivery. CONCLUSIONS: Infants who were < or = 32 weeks' gestation and remotely treated with antenatal steroids (average 21 days) had a significantly lower respiratory compliance compared with matched infants who were ideally treated with antenatal steroids. We speculate that the lower respiratory system compliance may reflect the dissipation of beneficial effects of antenatal steroids on pulmonary function when delivery occurs > 7 days after therapy and particularly when therapy is > 14 days before delivery.