Diane Schilling

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 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.

Acute effects of vecuronium on pulmonary function and hypoxemic episodes in preterm infants

Background: Varying effects of pancuronium on neonatal pulmonary mechanics have been documented, including a decrease in pulmonary compliance or no significant change in compliance; but measurements of respiratory mechanics or quantification of episodes of hypoxemia in preterm newborns receiving vecuronium (Norcuron, Bedford Labs, Bedford, OH, USA) have not been reported. The objective of the present study was to quantify the short‐term effects of vecuronium on pulmonary mechanics and episodes of hypoxemia in preterm infants receiving mechanical ventilation.

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

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.

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.

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

ObjectiveTo 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).MethodsSecondary 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.ResultsForty-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).ConclusionInfants treated with rescue antenatal steroids have a significantly higher respiratory compliance if delivery occurs within 7 days after treatment.