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.

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).

Medical advocacy among African-American women diagnosed with breast cancer: from recipient to resource.

PURPOSE: Medical advocacy at multiple levels (self, community/interpersonal, national/public health interest) may be helpful to address the disproportionate burden of breast cancer African-American women encounter. Little, however, is known about the interplay of medical advocacy at different levels. METHODS: We analyzed qualitative data from two studies focused on the psychosocial experiences of breast cancer among 38 African-American women living in Western Washington State. RESULTS: Emergent themes suggested that survivors received community/interpersonal advocacy from different members of social networks in the form of social support (appraisal, emotional, informational, instrumental). Survivors indicated that receiving this support was associated with greater self-advocacy in terms of their own care experiences, as well as greater community/interpersonal advocacy on their part as resources to other women diagnosed with breast cancer, their family, friends, and larger communities. CONCLUSION: Our findings suggest that community/interpersonal advocacy, including providing different types of support, may lead to improved self-advocacy as well as health-protective impacts for the networks in which survivors are embedded. Future quantitative research is warranted to support these findings and assess how this interplay is associated with improved outcomes among this marginalized and resilient population.

Revisiting Anticoagulation in Spine Surgery: Balancing Venous Thromboembolic Events and Epidural Hematoma.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: Venous thromboembolic events (VTE) and post-operative epidural hematoma (EDH) are significant complications after spine surgery. Guidelines for chemoprophylaxis are controversial and variability amongst surgeons remains. The objective of this study was to establish the incidence of clinical VTE and EDH at our institution and evaluate the association of chemoprophylaxis with clinical VTE and EDH. METHODS: We conducted a retrospective cohort study of patients undergoing spine surgery at a high-volume tertiary care center in Seattle, WA between January 2016 and December 2019. The Premier Health Care Database and Agency for Healthcare Research and Quality (AHRQ) patient indicators PSI-9 (Perioperative hemorrhage and hematoma) and PSI-12(Perioperative PE or DVT) were used to identify patients experiencing VTE and/or post-operative EDH. The primary outcome was the incidence of clinical VTE and EDH in post-operative spine patients. Secondary outcomes included the association of chemoprophylaxis with clinical VTE and EDH. RESULTS: From 2016 to 2019, 4587 patients underwent spine surgery, totaling 4764 hospital stays. The incidence of clinical VTE was .21% (10/4764) and the incidence of EDH was .10% (5/4764). Most hemorrhages occurred prior to the initiation of chemoprophylaxis. One patient with EDH received chemoprophylaxis prior to hemorrhage. CONCLUSIONS: The rate of post-operative clinical VTE and EDH in spine surgery is low. Despite early initiation of chemoprophylaxis after major spine surgery we did not appreciate a high rate of EDH. We attribute our low rate of clinical VTE to multimodal prophylaxis with SCDs, early mobilization and chemoprophylaxis on post-operative day 1.

Maternal Prenatal Hair Cortisol Is Associated with Child Wheeze among Mothers and Infants with Tobacco Smoke Exposure and Who Face High Socioeconomic Adversity.

The association of co-occurring prenatal stress and tobacco exposures on childhood wheezing and asthma are not well established. In this study, we compared maternal prenatal hair cortisol concentration (HCC) to the maternal report of infant wheezing (y/n) in the first year of life among mother-infant dyads exposed to tobacco smoke and socioeconomic adversity. Data were obtained from the Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function study. Maternal adversity was defined by the level of education, household income, and health insurance provider. Hair was collected at delivery, representing average circulating third-trimester cortisol levels. HCC was log transformed and dichotomized into high/low cortisol groups that were placed into a multivariate model predicting wheeze. Subjects (n = 132) were primarily White with ≤high school education and receiving government-provided health insurance. Forty-five percent of infants wheezed. Average HCC was 3.39 pg/mg hair. Women with HCC > 3.55 pg/mg were more than twice as likely to report having a child who wheezed (odds ratio 2.56, 95% confidence interval 1.22-5.40; p = 0.01), adjusting for insurance provider and maternal asthma. Among this sample of dyads with prenatal smoke exposure, elevated maternal HCC was associated with child wheeze that was not diminished after consideration of covariates.

Risk of metabolic syndrome and metabolic phenotypes in relation to biomarker-calibrated estimates of energy and protein intakes: an investigation from the Women's Health Initiative.

BACKGROUND: Metabolic syndrome (MetS) is associated with increased mortality independent of BMI, resulting in discordant metabolic phenotypes, such as metabolically healthy obese and metabolically unhealthy normal-weight individuals. Studies investigating dietary intake in MetS have reported mixed results, due in part to the limitations of self-reported measures. OBJECTIVES: To investigate the role of biomarker-calibrated estimates of energy and protein in MetS and metabolic phenotypes. METHODS: Postmenopausal participants from the Women's Health Initiative (WHI) study who were free of MetS at baseline, had available data from FFQs at baseline, and had components of MetS at Year 3 (n = 3963) were included. Dietary energy and protein intakes were estimated using biomarker calibration methods. MetS was defined as 3 or more of the following: elevated serum triglycerides (≥150 mg/dL), low HDL cholesterol (<50 mg/dL), hypertension [systolic blood pressure (BP) ≥130 or diastolic BP ≥85 mmHg], elevated serum glucose (>100 mg/dL), and abdominal adiposity (waist circumference > 89 cm). Models were adjusted for age, WHI study component, race/ethnicity, education, income, smoking, recreational physical activity, disease history, and parity. RESULTS: For every 10% increment in total calibrated energy intake, women were at a 1.37-fold elevated risk of MetS (95% CI, 1.15-1.63); a 10% increment in calibrated total protein intake was associated with a 1.21-fold elevated risk of MetS (95% CI, 1.00-1.47). Specifically, animal protein intake was associated with MetS (OR, 1.08; 95% CI, 1.02-1.14), whereas vegetable protein intake was not (OR, 0.99; 95% CI, 0.95-1.03). No differences were seen when examining metabolic phenotypes. CONCLUSIONS: We found that higher calibrated total energy, total protein, and total animal protein intakes were strongly associated with MetS. If replicated in clinical trials, these results will have implications for the promotion of energy and animal protein restrictions for the reduction of MetS risks.

Smoking cessation in pregnancy: a continuing challenge in the United States.

Despite significant population level declines, smoking during pregnancy remains a major public health issue in the United States (US). Approximately 360,000-500,000 smoke-exposed infants are born yearly, and prenatal smoking remains a leading modifiable cause of poor birth outcomes (e.g. birth < 37 gestational weeks, low birth weight, perinatal mortality). Women who smoke during pregnancy are more likely to be younger and from disadvantaged socioeconomic and racial and ethnic groups, with some US geographic regions reporting increased prenatal smoking rates since 2000. Such disparities in maternal prenatal smoking suggests some pregnant women face unique barriers to cessation. This paper reviews the current state and future direction of smoking cessation in pregnancy in the US. We briefly discuss the etiology of smoking addiction among women, the pathophysiology and effects of tobacco smoke exposure on pregnant women and their offspring, and the emerging issue of electronic nicotine delivery systems. Current population-based and individual smoking cessation interventions are reviewed in the context of pregnancy and barriers to cessation among US women. Finally, we consider interventions that are on the horizon and areas in need of further investigation.

Quantification of nutritive sucking among preterm and full-term infants.

PURPOSE: We developed summaries of oral bottle-feeding skills among preterm (<37 gestational weeks) and full-term (≥37 gestational weeks) infants using a mechanical device (Orometer) to measure intraoral pressure changes, with accompanying automated software and analytics. We then compared the rates of change in feeding skills over several weeks (feeding trends) between preterm and full-term infants. We also compared group means at 40 weeks post menstrual age (PMA). PATIENTS AND METHODS: Healthy full-term and preterm infants capable of oral feeding were recruited from the Pediatric Outpatient Clinic at University of California San Francisco, Fresno, and from the Oregon Health & Science University Doernbecher Neonatal Critical Care Unit, respectively. Feeding skill was quantified using an Orometer and automated suck-analysis software. Factor analysis reduced the >40 metrics produced by the Orometer system to the following seven factors that accounted for >99% of the sample covariance: suck vigor, endurance, resting, irregularity, frequency, variability, and bursting. We proposed that these factors represent feeding skills and they served as the dependent variables in linear models estimating trends in feeding skills over time for full-term and preterm infants (maturation). At approximately 40 weeks PMA we compared mean feedings skills between infants born preterm and those born full-term using predictions from our models. RESULTS: Feeding skills for 117 full-term infants and 82 preterm infants were first captured at mean PMA of 42.3 and 36.0 weeks, respectively. For some feeding skills, preterm and full-term infants showed different trends over time. At 37-40 weeks PMA, preterm infants took approximately 15% fewer sucks than infants born full-term (p=0.06) and generally had weaker suck vigor, greater resting, and less endurance than full-term babies. Preterm infant-feeding skills appeared similar to those of full-term infants upon reaching ≥40 weeks PMA, although preterm infants showed greater variability for all factors. CONCLUSION: The Orometer device, accompanying software, and analytic methods provided a framework for describing trends in oral feeding, thereby allowing us to characterize differences in maturation of feeding between healthy preterm and full-term infants.

Maternal high-fat diet in mice leads to innate airway hyperresponsiveness in the adult offspring.

Maternal obesity prior to and during pregnancy has been associated with an increased incidence of childhood asthma. As diets rich in saturated fat are linked to obesity and inflammation, we created a murine model to investigate the effect of maternal high-fat diet (HFD) on adult offspring airway hyperreactivity (AHR), a cardinal feature of asthma. Balb/cByJ dams were fed a HFD (60% fat Calories) or normal-fat diet (NFD) (10% fat Calories) from 8 weeks prior to first breeding through their pregnancies. Pups were weaned to either a HFD or NFD (at 4 weeks of age). AHR was measured in the 10-week-old offspring following inhaled methacholine challenge by end-inflation technique. Bronchial alveolar lavage fluid (BALF) was analyzed for cell count, total protein, and IL-6. Offspring of HFD dams weaned to NFD had increased AHR compared to offspring of NFD dams weaned to NFD Offspring of HFD dams that remained on HFDs had increased AHR compared to offspring of NFD dams weaned to HFDs. Offspring of HFD dams had higher BALF cell counts, higher neutrophil percentage, greater total protein, and IL-6 in the BALF These results demonstrate that a maternal diet high in saturated fat through pregnancy and lactation plays a key role in programming adult offspring AHR.

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.