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 daily vitamin C would have improved pulmonary function tests (PFTs) and decreased wheezing compared to those randomized to placebo. Design, Setting, Participants, Intervention Randomized, double-blind trial in three sites in the Pacific Northwest. Between March 2007 and January 2011, 206 pregnant smokers were recruited and 179 randomized to vitamin C (500 mg/day) versus placebo (89 to vitamin C and 90 to placebo). 159 newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through one year of age and PFTs were done at one year of age. Main Outcomes and Measures The primary outcome was measurements of newborn pulmonary function (specifically the 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 one year of age and PFTs at one year of age. A subgroup of pregnant smokers and nonsmokers had genotyping performed. Results Newborns of women randomized to vitamin C (n= 76) had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345; adjusted 95% confidence interval [CI] for difference 0.011, 0.062; p =0.006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg; 95% CI 0.02, 0.20; p =0.012) than those randomized to placebo (n=83). Offspring of women randomized to vitamin C had significantly decreased wheezing through 1 year of age (15/70 [21%] vs 31/77 [40%]; relative risk 0.56, 95% CI 0.33, 0.95; p =0.03). There were no significant differences in the one year PFTs between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the alpha 5 nicotinic receptor (rs16969968) (p value for interaction = 0.0006). Conclusion and Relevance Supplemental vitamin C to pregnant smokers improved newborn PFTs 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

Objective-To compare respiratory compliance (Crs) and functional residual capacity (FRC) in infants randomized to a rescue course of antenatal steroids (AS) versus placebo.Study Design-Randomized, double-blinded trial. Pregnant women ≥ 14 days after initial AS were randomized to rescue AS or placebo. The primary outcomes were measurements of Crs and FRC. This study is registered with clinicaltrials.gov [NCT00669383].Results-44 mothers (56 babies) received rescue AS and 41 mothers (57 babies) received placebo. There was no significant difference in birth weight, or head circumference. Infants in the rescue group had an increased Crs (1.21 versus 1.01 mL/cm H 2 O/kg; adjusted 95% CI 0.01, 0.49; p =0.0433) compared to placebo. 13% in the rescue versus 29% in the placebo group required ≥ 30% oxygen (p <0.05). Patients delivered at ≤ 34 weeks had greater pulmonary benefits.Conclusion-Infants randomized to rescue AS have a significantly increased Crs compared to placebo.

Objective To compare pulmonary function testing including respiratory compliance (Crs) and time to peak tidal expiratory flow: 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 FiO2) 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 H2O/kg; p<0.02) and decreased Tptef:Te (0.308 vs 0.423; p<0.01) when compared with the term infants. Late preterm infants also had an increased respiratory resistance (0.064 vs 0.043 cm H2O/mL/sec; p<0.01). 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.

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. OBJECTIVETo 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 MEASURESThe 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 H 2 O/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.

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.

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 a5 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 FEF 75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF 50 and FEF 25-75 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 FEF 75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, 23.33 to 35.64; P = 0.10), FEF 50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF 25-75 (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 a5 nicotinic acetylcholine receptor (rs16969968).Conclusions: Although the primary outcome of FEF 75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF 50 and FEF 25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF 50 and FEF 25-75 ) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT 01723696).

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 ³24 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 ³ 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.

BackgroundVitamin 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.ObjectiveTo assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age.MethodsThis 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.ResultsFEFs 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).ConclusionsIn 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.