Grandmaternal pre-pregnancy body mass index and infant birthweight: a mediation analysis of maternal pre-pregnancy body mass index.

The objectives of this study were to examine the total effect of grandmaternal [G0] pre-pregnancy body mass index (BMI) on infant [G2] birthweight z-score and to quantify the mediation role of maternal [G1] pre-pregnancy BMI. Data were extracted from the Nova Scotia 3G Multigenerational Cohort. The association between G0 pre-pregnancy BMI and G2 birthweight z-score and the mediated effect by G1 pre-pregnancy BMI were estimated using g-computation with adjustment for confounders identified using a directed acyclic graph and accounting for intermediate confounding. 20822 G1-G2 dyads from 18450 G0 were included. Relative to G0 normal weight, G0 underweight decreased mean G2 birthweight z-score (-0.11, 95% confidence interval (CI) -0.20, -0.030), while G0 overweight and obesity increased mean G2 birthweight z-score (0.091 [95% CI 0.034, 0.15] and 0.22 [95% CI 0.11, 0.33]). G1 pre-pregnancy BMI partly mediated the association, with the largest effect size observed for G0 obesity (0.11, 95% CI 0.080, 0.14). Estimates of the direct effect were close to the null. In conclusion, grandmaternal pre-pregnancy BMI was associated with infant birthweight z-score. Maternal pre-pregnancy BMI partly mediated the association, suggesting that factors related to BMI may play an important role in the transmission of weight across the maternal line.

A Postpartum Perineal Clinic in Nova Scotia: Characteristics Associated With Attendance and Its Association With Recurrent Obstetrical Anal Sphincter Tears.

OBJECTIVES: The Healthy Recovery after Childbirth Clinic (HRCC) in Nova Scotia provides postpartum care to patients who experience obstetric anal sphincter injuries (OASIS). The purpose of this study was to describe characteristics associated with HRCC attendance, characteristics associated with a trial of labour in a subsequent delivery, and OASIS recurrence by HRCC attendance status. METHODS: A retrospective cohort study using the Atlee Perinatal Database and clinical record review included primiparous individuals who sustained an OASIS at IWK Health in Halifax between 2013 and 2020. The χ2 and Fisher exact tests were performed to compare groups. RESULTS: Of the 1041 individuals included, 67% attended HRCC. Attendance increased from 58% in 2013-2015 to 77% in 2019-2020. Younger age (<25 years) and smoking were associated with lower HRCC attendance (P = 0.07 and <0.01, respectively). Other characteristics, including area-level income and driving distance to HRCC, were not associated with attendance (P > 0.05). Of the 439 individuals who had a subsequent delivery, 92% had a trial of labour. Individuals with fourth-degree injury were less likely to attempt a trial of labour than those with third-degree injury (73% vs. 94%, P < 0.01). Of those who delivered vaginally, OASIS recurrence was similar in those who did and did not attend the HRCC (7.5% vs. 6.5%, P = 0.84). CONCLUSIONS: HRCC attendance was high, but the disparity by age and smoking status suggests some barriers to access that should be explored. Although we found no difference in OASIS recurrence by HRCC attendance, more research with larger samples with adjustment for confounders is needed.

Health Care Utilization in the First 7 Years in Children with Fetal Growth Abnormalities: A Retrospective Cohort Study.

OBJECTIVE: To investigate the relationship between birth weight for gestational age and health care utilization of term offspring from birth to 7 years. STUDY DESIGN: We used a population-based retrospective cohort study of infants (≥37 weeks' gestational age) born between 2003 and 2007 in the Canadian province of Nova Scotia (n = 42 050). Perinatal records were linked to provincial administrative health data from birth to age 7 years. The primary outcome was health care utilization (physician visits and hospital admissions) and costs. Birth weight was categorized as small for gestational age (SGA, <10th percentile), appropriate for gestational age (AGA), or large for gestational age (LGA, >90th percentile). Regression models adjusted for potential confounders were used to investigate the associations. RESULTS: Children born SGA had a higher number of specialist visits and hospital admissions, a longer length of stay for the birth admission, and, as a result, higher physician and hospital costs amounting to a cost differential of Can $1222 during the first 7 years of life compared with children born AGA. By contrast, health care use and costs did not differ between children born LGA and AGA. CONCLUSION: Former SGA term infants have a moderate increase in health care use and costs in early childhood compared with former AGA infants, and LGA birth at term is not associated with higher health care utilization.

Revisiting Risk and Benefit in Early Oncology Trials in the Era of Precision Medicine: A Systematic Review and Meta-Analysis of Phase I Trials of Targeted Single-Agent Anticancer Therapies.

PURPOSE: Phase I trials are a crucial step in the evaluation of new cancer therapies. Historically, low rates of response (5%) and comparably high rates of death from toxicities (0.5%) have contributed to debates on the ethics and orientation of these trials. With the introduction of novel targeted therapies, a contemporary estimate is needed. METHODS: We systematically searched PubMed, Embase, and ClinicalTrials.gov for reports of phase I oncology trials of single-agent targeted immunomodulators, molecularly targeted therapies, and antiangiogenic agents, published between January 2015 and July 2018. Adult and pediatric trials of solid and hematological malignancies were eligible. Treatment-related adverse events (grades 3, 4, and 5) and response rates (objective, complete, and partial) were extracted and analyzed. RESULTS: One hundred and fifty-eight trial reports, covering 6,707 patients, were included. The rate of treatment-related deaths was 0.0% (95% CI, 0.0 to 0.1), while 13.2% of patients (9.5 to 17.3) experienced a grade 3 or 4 treatment-related toxicity. The combined objective response rate was 6.4% (4.6 to 8.5). Among trials using tumor biomarkers as eligibility criteria, the objective response rate was higher (12.0% [7.3 to 17.6] compared to 4.9% [2.5 to 5.7], P value < .01). The same was true of trials focusing on a single tumor type (13.4% [8.2 to 19.4]) compared to multiple tumor types (3.8% [2.5 to 5.3], P value < .01). CONCLUSION: Reduced grade 5 risk and improved benefit appears to exist in modern phase I oncology trials, particularly in trials that target single tumor types and integrate biomarkers as eligibility criteria. These findings provide information to support informed consent discussions, highlight the need for improved reporting of phase I oncology trials, and provide direction for optimizing their design.

Incidence, Intrapartum Risk Factors, and Prognosis of Neonatal Hypoxic-Ischemic Encephalopathy Among Infants Born at 35 Weeks Gestation or More.

INTRODUCTION: Neonatal hypoxic-ischemic encephalopathy (HIE) is associated with neonatal mortality, acute neurological injury, and long-term neurodevelopmental disabilities; however, the association between intrapartum factors and HIE remains unclear. METHODS: This population-based cohort study used linked obstetrical and newborn data derived from the Nova Scotia Atlee Perinatal Database (NSAPD, 1988-2015) and the AC Allen Perinatal Follow-Up Program Database (2006-2015) for all pregnancies with live, non-anomalous newborns ≥35 weeks gestation, not delivered by pre-labour cesarean section. Temporal trends in HIE incidence were described, and logistic regression estimated odds ratios (OR) with 95% confidence intervals (CI) for the association of intrapartum factors with HIE. RESULTS: The NSAPD identified 227 HIE cases in the population of 226 711 deliveries from 1988 to 2015. Women with clinical chorioamnionitis in labour (OR 8.0; 95% CI 3.9-16), emergency cesarean delivery (OR 10; 95% CI 7.6-14), shoulder dystocia (OR 3.5; 95% CI 2.1-5.7), placental abruption (OR 18; 95% CI 11-29), and cord prolapse (OR 30; 95% CI 15-61) were more likely to have newborns with HIE. Two-thirds of newborns with HIE had an abnormal intrapartum fetal heart rate tracing. The mortality rate among infants with HIE was 27% by 3 years of age. Neurodevelopmental outcomes in the surviving infants were normal in 43% and showed severe developmental delay in 40%. CONCLUSION: Overall, the rate of HIE was low in infants born at ≥35 weeks gestation. The identification of associated intrapartum factors should promote increased surveillance in these clinical situations and emphasize the importance of careful management to optimize newborn outcomes.

Enteral nutrition for intubated adults in the intensive care unit prior to general anesthesia: a scoping review.

OBJECTIVE: The objective of this scoping review was to examine and map fasting times for intubated adult patients in the intensive care unit prior to general anesthesia, and patient outcomes following the cessation of enteral nutrition. BACKGROUND: Malnutrition in critically ill patients in the intensive care unit has been associated with increased infectious morbidity, increased length of intensive care unit and hospital stay, increased rate of infections, increased number of ventilator days, and impaired wound healing. One potential contributor to malnutrition is prolonged fasting times prior to general anesthesia. The American Society of Parenteral and Enteral Nutrition and the Society of Critical Care Medicine recommend minimizing fasting times prior to surgery; however, neither gives guidelines for intubated patients in the intensive care unit. By limiting fasting times with cuffed endotracheal tubes, nutritional goals could be improved without additional complications. INCLUSION CRITERIA: This scoping review considered studies that included patients in the intensive care unit who were 18 years and older possessing a cuffed endotracheal tube, requiring enteral nutrition, and undergoing surgery requiring general anesthesia. Specifically, fasting protocols, location of enteral nutrition being delivered, and patient outcomes were mapped for studies meeting these criteria. The review also looked at available protocols for preoperative fasting times for patients with cuffed endotracheal tubes prior to surgical procedures requiring anesthesia. METHODS: The JBI methodology was followed to complete this scoping review. The objectives, inclusion criteria, and methods of analysis for this review were previously established and documented in an a priori protocol. RESULTS: Three studies, one prospective observational study, and two retrospective chart reviews, with a total of 128 participants, were included in this review. Also, eight fasting protocols regarding adult intensive care unit patients with cuffed endotracheal tubes prior to general anesthesia were identified. CONCLUSIONS: The identified studies and protocols conclude that institutions apply different fasting times depending on procedure types and feeding access for patients with cuffed endotracheal tubes. Some protocols require fasting to begin at midnight on the day of the procedure, while others allow enteral nutrition to be continued throughout the procedure. All identified protocols exclude some procedures from a reduced fast, typically airway procedures and abdominal surgeries. Each institution has specific requirements for patients that qualify for a reduced fast - such as feeding tube location, type of procedure, and positioning during the procedure - as well as specific times for enteral nutrition to be held. Following review of the studies, no aspiration events were witnessed during any operative procedure where a reduced fast was used.

Birth by Caesarean section and otitis media in childhood: a retrospective cohort study.

The objective of the present study was to examine the association between birth by Caesarean section (CS) and otitis media (OM) in childhood. We assembled a retrospective cohort of children born between 2003 and 2007 in Nova Scotia and followed them through to 2014. The cohort was derived through a linkage of the Nova Scotia Atlee Perinatal Database with provincial administrative health data. Cox proportional hazards, negative binomial regression and logistic regression were used to examine the association between CS and OM. Among the 36,318 children, 27% were born by CS, and 78% had at least one OM episode (median 2 episodes). Children born by CS were at a slightly higher risk of OM (hazard ratio 1.06, 95% confidence interval (CI) 1.03, 1.09), had more OM episodes in the first 7 years of life (incidence rate ratio 1.04, 95% CI 1.01, 1.07), and were more likely to be above the 95th percentile for OM episodes than children born vaginally (odds ratio 1.10, 95% CI 0.99, 1.23). Our study shows that birth by CS is weakly associated with OM in childhood, but the clinical and public health impact of these findings is small.

The 3G Multigenerational Cohort of Nova Scotian women and their mothers and offspring.

BACKGROUND: The negative impact of exposures such as maternal obesity, excessive gestational weight gain, and hypertension in pregnancy on the health of the next generation has been well studied. Evidence from animal studies suggests that the effects of in utero exposures may persist into the second generation, but the epidemiological literature on the influence of pregnancy-related exposures across three generations in humans is sparse. OBJECTIVES: This cohort was established to investigate associations between antenatal and perinatal exposures and health outcomes in women and their offspring. POPULATION: The cohort includes women who were born and subsequently had their own pregnancies in the Canadian province of Nova Scotia from 1980 onward. DESIGN: Intergenerational linkage of data in the Nova Scotia Atlee Perinatal Database was used to establish a population-based dynamic retrospective cohort. METHODS: The cohort has prospectively collected information on sociodemographics, maternal health and health behaviours, pregnancy health and complications, and obstetrical and neonatal outcomes for two generations of women and their offspring. PRELIMINARY RESULTS: As of October 2018, the 3G cohort included 14 978 grandmothers (born 1939-1986), 16 766 mothers or cohort women (born 1981-2003), and 28 638 children (born 1996-2018). The cohort women were generally younger than Nova Scotian women born after 1980, and as a result, characteristics associated with pregnancy at a younger age were more frequently seen in the cohort women; sampling weights will be created to account for this design effect. The cohort will be updated annually to capture future deliveries to women who are already in the cohort and women who become eligible for inclusion when they deliver their first child. CONCLUSIONS: The 3G Multigenerational Cohort is a population-based cohort of women and their mothers and offspring, spanning a time period of 38 years, and provides the opportunity to study inter- and transgenerational associations across the maternal line.

Cesarean Delivery and Healthcare Utilization and Costs in the Offspring: A Retrospective Cohort Study.

OBJECTIVE: To examine the association between cesarean delivery and healthcare utilization and costs in offspring from birth until age 7 years. STUDY DESIGN: A retrospective cohort study of singleton term births in the Canadian province of Nova Scotia between 2003 and 2007 followed until age 7 years was conducted using data from the Nova Scotia Atlee Perinatal Database and administrative health data. The main exposure was mode of delivery (cesarean delivery vs vaginal birth); the outcome was healthcare utilization and costs during the first 7 years of life. Associations were modeled using multiple regression adjusting for maternal prepregnancy weight and sociodemographic factors. RESULTS: In total, 32 464 births were included in the analysis. Compared with children born by vaginal birth, children born by cesarean delivery had more physician visits (incidence rate ratio 1.06, 95% CI 1.05-1.08) and longer hospital stays (incidence rate ratio 1.12, 95% CI 1.03-1.21) and were more likely to be high utilizers of physician visits (OR 1.23, 95% CI 1.10-1.37). Physician and hospital costs were $775 higher for children born by cesarean delivery compared with vaginal birth. CONCLUSIONS: Cesarean delivery compared with vaginal birth is associated with small but statistically significant increases in healthcare utilization and costs during the first 7 years of life.

Birth weight for gestational age and the risk of asthma in childhood and adolescence: a retrospective cohort study.

OBJECTIVE: To examine the association between birth weight for gestational age and asthma in childhood and adolescence while controlling for potential confounders and considering smoking as an effect modifier. METHODS: A retrospective cohort of all singleton term births in Nova Scotia, Canada, between 1989 and 1993 was identified in the provincial perinatal database and followed through 2014 by linking with administrative health data. The outcome, asthma, was defined as having one hospitalisation or two physician visits with an International Classification of Diseases code for asthma in a 2-year period. Birth weight was categorised as small (SGA), large (LGA) or appropriate (AGA) for gestational age. Multivariable-adjusted Cox proportional hazards models were used to examine the association between the birth weight for gestational age and asthma and to test for effect modification by maternal smoking in pregnancy. RESULTS: Of the 40 724 cohort children, 10.5% and 11.7% were born SGA and LGA, respectively, and the risk of developing asthma to age 18 years was 30.2%. The adjusted HRs for SGA and LGA (relative to AGA) and asthma were 1.07 (95% CI 1.02 to 1.14) and 0.96 (95% CI 0.91 to 1.02), respectively. Relative to AGA children born to non-smoking mothers, SGA children were not at increased risk of asthma (HR 1.02), whereas both AGA and SGA children born to smoking mothers were at significantly increased risk (HR 1.14 and 1.29, respectively). CONCLUSIONS: Our findings suggest that SGA in term infants is not associated with asthma in childhood in the absence of smoking in pregnancy.

Maternal pre-pregnancy obesity and health care utilization and costs in the offspring.

BACKGROUND/OBJECTIVE: The association between maternal pre-pregnancy obesity and adverse child health outcomes is well described, but there are few data on the relationship with offspring health service use. We examined the influence of maternal pre-pregnancy obesity on offspring health care utilization and costs over the first 18 years of life. METHODS: This was a population-based retrospective cohort study of children (n = 35,090) born between 1989 and 1993 and their mothers, who were identified using the Nova Scotia Atlee Perinatal Database and linked to provincial administrative health data from birth through 2014. The primary outcome was health care utilization as determined by the number and cost of physician visits, hospital admissions and days, and high utilizer status (>95th percentile of physician visits). The secondary outcome was health care utilization by ICD chapter. Maternal pre-pregnancy weight was categorized as normal weight, overweight, or obese. Multivariable-adjusted regression models were used to examine the association between maternal weight status and offspring health care use. RESULTS: Children of mothers with pre-pregnancy obesity had more physician visits (10%), hospital admissions (16%), and hospital days (10%) than children from mothers of normal weight over the first 18 years of life. Offspring of mothers with obesity had C$356 higher physician costs and C$1415 hospital costs over 18 years than offspring of normal weight mothers. Children of mothers with obesity were 1.74 times more likely to be a high utilizer of health care and had higher rates of physician visits and hospital stays for nervous system and sense organ disorders, respiratory disorders, and gastrointestinal disorders compared to children of normal weight mothers. CONCLUSION: Our findings suggest that maternal pre-pregnancy overweight and obesity are associated with slightly higher offspring health care utilization and costs in the first 18 years of life.

Factors Associated with Trial of Labour and Mode of Delivery in Robson Group 5: A Select Group of Women With Previous Caesarean Section.

OBJECTIVE: To determine the proportion of women in Robson group 5 (RG5) who were eligible for a trial of labour after Caesarean (TOLAC) and, among eligible candidates, identify determinants of having a TOLAC and subsequent vaginal delivery (VD). METHODS: This population-based cohort study used data derived from the Nova Scotia Atlee Perinatal Database. Deliveries from 1998-2014 to women in RG5 (≥1 previous CS with a singleton term cephalic fetus) were included. Eligibility for a TOLAC was based on SOGC criteria. Multivariable logistic regression was used to identify characteristics independently associated with TOLAC and VD. The characteristics associated with VD were used in a logistic model to predict the theoretical probability of VD in women who did not have a TOLAC. RESULTS: Of the 15 111 deliveries in RG5, 75.3% were by CS. Of the 14 763 eligible women, 5488 (37.2%) had a TOLAC, of which 3739 (68.1%) resulted in VD. Predictors of VD included high area-level income and either a CS without labour or a spontaneous VD in the preceding pregnancy. While mode of previous delivery also predicted TOLAC among eligible women, high area-level income was associated with reduced odds of TOLAC. The probability of VD in women who did not undergo TOLAC was estimated to be 47.1%, and the lowest CS rate attainable in RG5 was estimated at 46.3%. CONCLUSIONS: Sociodemographic factors such as income and previous mode of delivery were associated with the rates of TOLAC and subsequent VD in eligible women, and suggest that the Caesarean section rate in RG5 could be safely reduced.

Neonatal Intensive Care Unit Boot Camp: A Preparatory Curriculum for Pediatric Residents.

Introduction: Resident training has changed significantly in recent years, resulting in reduced experiences and practice. Because pediatric residents have fewer required intensive care unit (ICU) rotations, we introduced a neonatal ICU (NICU) boot camp (2014-2015) that continues today to prepare residents immediately prior to beginning an NICU rotation. Methods: The NICU boot camp consists of three 1-hour sessions: two interactive lectures with case-based application and one hands-on, integrative learning using simulation. The sessions are designed to cover basic information to assist in daily rounding and decision making while in the NICU. After their NICU rotation, residents complete a 12-item questionnaire. Program evaluation includes direct observation during sessions, faculty debriefing, and a postprogram resident survey. Results: Fifty-seven residents participated; questionnaire responses were available from 46 (80.70%). Combined percentages of very useful and extremely useful responses for the three sessions were 82.61%, 78.26%, and 82.60%, with 86.95% for the overall program; 80.40% agreed that repeating boot camp prior to each NICU rotation would be useful. Analysis of narrative responses revealed that participation in boot camp enhanced residents' readiness and confidence for patient care in the NICU and as stated for each educational objective. Discussion: Program evaluation results support highly effective and sustainable implementation and achievement of educational objectives. Minor refinements continue for enhancing active learning and content materials and for increasing rigor of program evaluation. Results also suggest that our boot camp may benefit other pediatric programs and serve as a model for use in other resident specialty programs.

Associations between postmenopausal endogenous sex hormones and C-reactive protein: a clearer picture with regional adiposity adjustment?

OBJECTIVE: To better understand the pathogenesis of inflammatory-related diseases after menopause, we studied the adiposity-independent association between endogenous sex hormones and C-reactive protein (CRP), a biomarker of inflammation. METHODS: We conducted a secondary, cross-sectional analysis of baseline data from the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2007), including 319 healthy, postmenopausal women not using hormone therapy. Multivariable linear regression models related serum CRP levels to estrogens, androgens, and sex hormone-binding globulin (SHBG), all on the natural logarithmic scale. Models were adjusted for age, lipids, medication, and former menopausal hormone therapy use, and also for adiposity (body mass index [BMI], per cent body fat [via whole-body dual x-ray absorptiometry], or intra-abdominal fat area [via computed tomography]). RESULTS: Without adiposity adjustment, estrone, total estradiol, and free estradiol were significantly positively associated with CRP, whereas SHBG was significantly inversely associated with CRP. Of all adiposity measures, adjustment for BMI caused the greatest attenuation of CRP-estrogen associations; only free estradiol (ß = 0.24, 95% confidence interval [CI] 0.06, 0.43) and SHBG (ß = -0.37, 95% CI -0.60, -0.13) associations remained significant. Inverse associations between CRP-total testosterone became stronger with BMI adjustment (ß = -0.20, 95% CI -0.40, -0.01). Differential associations across categories of BMI, former hormone therapy use, and years since menopause were suggestive, but not statistically significant (Pheterogeneity > 0.05). CONCLUSIONS: Prospective and systems epidemiological studies are needed to understand whether or not the cross-sectional associations we observed, independent of adiposity, between CRP-SHBG, CRP-total testosterone, and CRP-free estradiol, are causal.

Determinants of vitamin D status in pregnant women and neonates.

OBJECTIVES: Evidence suggests a beneficial effect of vitamin D on perinatal health; however, low vitamin D status is prevalent in pregnant women and neonates. The objective was to determine factors that are associated with vitamin D status of mothers in early pregnancy and neonates. METHODS: The study comprised 1,635 pregnant women from Quebec City and Halifax, Canada, 2002-2010. Vitamin D status was based on the concentration of 25-hydroxy-vitamin D [25(OH)D] determined with a chemiluminescence immunoassay in maternal sera collected at a median of 15 weeks' gestation and in neonatal cord sera at delivery. A questionnaire with information on potential determinants was completed midpregnancy. RESULTS: A total of 44.8% of mothers and 24.4% of neonates had 25(OH)D concentrations <50 nmol/L. Adjusted mean (95% confidence interval) maternal 25(OH)D levels were higher in summer than in winter by 16.1 nmol/L (13.6-18.7), and in those in the highest versus the lowest category of education by 6.1 nmol/L (0.5-11.8), in BMI <25 kg/m2 versus BMI ≥35 kg/m2 by 8.2 nmol/L (4.0-12.3), and in the highest versus the lowest physical activity category by up to 9.5 nmol/L (2.9-16.1). Determinants of neonatal 25(OH)D levels were similar but also included maternal age, dairy intake, supplement use and 25(OH)D level. CONCLUSION: This study suggests that vitamin D status of pregnant women and/or neonates might be improved through supplementation, adequate dairy intake, a move towards a healthy pre-pregnancy body weight, and participation in physical activity. Controlled studies are needed to determine the effectiveness of interventions aimed at these factors.

Effects of exercise on markers of oxidative stress: an Ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention Trial.

BACKGROUND: Oxidative stress may contribute to cancer aetiology through several mechanisms involving damage to DNA, proteins and lipids leading to genetic mutations and genomic instability. The objective of this study was to determine the effects of aerobic exercise on markers of oxidative damage and antioxidant enzymes in postmenopausal women. METHODS: The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA) was a two-centre, two-armed randomised trial of 320 inactive, healthy, postmenopausal women aged 50-74 years. Participants were randomly assigned to a year-long exercise intervention (225 min/week) or a control group while being asked to maintain a normal diet. Fasting blood samples were obtained and plasma concentrations of two oxidative damage markers (8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-Iso-PGF2α)) and two antioxidant enzymes (superoxide dismutase and catalase) were measured at baseline, 6 months and 12 months. Intention-to-treat (ITT) and per-protocol analyses were performed using linear mixed models adjusted for baseline biomarker concentrations. A further exercise adherence analysis, based on mean minutes of exercise per week, was also performed. RESULTS: In the ITT and per-protocol analyses, the exercise intervention did not have any statistically significant effect on either oxidative damage biomarkers or antioxidant enzyme activity. CONCLUSIONS: A year-long aerobic exercise intervention did not have a significant impact on oxidative stress in healthy, postmenopausal women. TRIAL REGISTRATION NUMBER: NCT00522262.

Impact of aerobic exercise on levels of IL-4 and IL-10: results from two randomized intervention trials.

The mechanisms whereby regular exercise reduces chronic inflammation remain unclear. We investigated whether regular aerobic exercise alters basal levels of interleukin (IL)-10 and IL-4 in two randomized trials of physical activity. The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA, n = 320) and the Breast Cancer and Exercise Trial in Alberta (BETA, n = 400) were two-center, two-armed randomized trials in inactive, healthy, postmenopausal women. Both trials included an exercise intervention prescribed five times/week and no dietary changes. In ALPHA, the exercise group was prescribed 225 min/week versus no activity in the controls. BETA examined dose-response effects comparing 300 (HIGH) versus 150 (MODERATE) min/week. Plasma concentrations of IL-10 and IL-4 were measured at baseline, 6, and 12 months. Intention-to-treat (ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. Circulating anti-inflammatory cytokine levels decreased among all groups, with percent change ranging from -3.4% (controls) to -8.2% (HIGH) for IL-4 and -1.6% (controls) to -7.5% (HIGH) for IL-10. No significant group differences were found for IL-4 (ALPHA P = 0.54; BETA P = 0.32) or IL-10 (ALPHA P = 0.84; BETA P = 0.68). Some evidence for moderation of the effect of exercise by baseline characteristics was found for IL-10 but not for IL-4. Results from these two large randomized aerobic exercise intervention trials suggest that aerobic exercise does not alter IL-10 or IL-4 in a manner consistent with chronic disease and cancer prevention.