Jennifer J. Stuart

Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia

OBJECTIVE: Observational studies suggest that serum levels of 25-hydroxyvitamin D (25[OH]D) are inversely associated with acute respiratory infections (ARIs). We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs. METHODS: By using cluster randomization, classrooms of 744 Mongolian schoolchildren were randomly assigned to different treatments in winter (January–March). This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk (control; n = 104) or milk fortified with 300 IU of vitamin D3 (n = 143). This comparison was double-blinded. The primary outcome was the number of parent-reported ARIs over the past 3 months. RESULTS: At baseline, the median serum 25(OH)D level was 7 ng/mL (interquartile range: 5–10 ng/mL). At the end of the trial, follow-up was 99% (n = 244), and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different (7 vs 19 ng/mL; P < .001). Compared with controls, children receiving vitamin D reported significantly fewer ARIs during the study period (mean: 0.80 vs 0.45; P = .047), with a rate ratio of 0.52 (95% confidence interval: 0.31–0.89). Adjusting for age, gender, and history of wheezing, vitamin D continued to halve the risk of ARI (rate ratio: 0.50 [95% confidence interval: 0.28–0.88]). Similar results were found among children either below or above the median 25(OH)D level at baseline (rate ratio: 0.41 vs 0.57; Pinteraction = .27). CONCLUSIONS: Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency.

Maternal Recall of Hypertensive Disorders in Pregnancy: A Systematic Review

BACKGROUND Hypertensive disorders in pregnancy are risk markers for future maternal coronary heart disease (CHD). Clinical assessment of a womans history of pregnancy complications relies on self-report, but the predictive value of maternal recall is unclear. A systematic review was conducted to comprehensively review and critically assess the available literature on maternal recall of hypertensive disorders in pregnancy. METHODS The PubMed, EMBASE, and Web of Science databases were searched through August 2012. We included original research articles comparing maternal recall of hypertensive disorders in pregnancy with medical records. RESULTS Ten studies met eligibility criteria for qualitative analysis and were independently reviewed by two investigators. Recall periods ranged from 48 hours to 30 years. Length of recall did not appear to uniformly affect recall quality. Sensitivity was generally lower and less consistent for gestational hypertension than for preeclampsia. Specificity was >90% for all hypertensive disorders. Determinants of recall accuracy included maternal education and parity. CONCLUSIONS Although maternal recall of hypertensive disorders of pregnancy is specific, low sensitivity and predictive values may limit the clinical utility of asking mothers to recall their history of hypertensive pregnancy complications. Future research on maternal recall of pregnancy complications should be designed to yield predictive values and test recall of disorder subtypes, recurrent complications, and changing recall over time in the same population. The utility of gestation length and offspring birth weight for clinical identification of women whose pregnancy history puts them at increased CHD risk should also be explored.

Preterm Delivery and Maternal Cardiovascular Disease in Young and Middle-Aged Adult WomenClinical Perspective

Background: Preterm delivery has been shown to be associated with increased risk of cardiovascular disease (CVD), but it is unknown whether this risk remains after adjustment for prepregnancy lifestyle and CVD risk factors. Methods: We examined the association between history of having delivered an infant preterm (<37 weeks) and CVD in 70 182 parous women in the Nurses’ Health Study II. Multivariable Cox proportional-hazards models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for CVD events (myocardial infarction and stroke, n=949); we also adjusted for intermediates to determine the proportion of the association between preterm and CVD accounted for by postpartum development of CVD risk factors. Results: After adjusting for age, race, parental education, and prepregnancy lifestyle and CVD risk factors, preterm delivery in the first pregnancy was associated with an increased risk of CVD (HR, 1.42; 95% CI, 1.16–1.72) in comparison with women with a term delivery (≥37 weeks) in the first pregnancy. When preterm delivery was split into moderate preterm (≥32 to <37 weeks) and very preterm (<32 weeks), the HRs were 1.22 (95% CI, 0.96–1.54) and 2.01 (95% CI, 1.47–2.75), respectively. The increased rate of CVD in the very preterm group persisted even among women whose first pregnancy was not complicated by hypertensive disorders of pregnancy (HR, 2.01; 95% CI, 1.38–2.93). In comparison with women with at least 2 pregnancies, all of which were delivered at term, women with a preterm first birth and at least 1 later preterm birth had a HR of CVD of 1.65 (95% CI, 1.20–2.28). The association between moderate preterm first birth and CVD was accounted for in part by the development of postpartum chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and changes in body mass index (proportion accounted for, 14.5%; 95% CI, 4.0–41.1), as was the very-preterm-CVD relationship (13.1%; 95% CI, 9.0–18.7). Conclusions: Preterm delivery is independently predictive of CVD and may be useful for CVD prevention efforts. Because only a modest proportion of the preterm-CVD association was accounted for by development of conventional CVD risk factors, further research may identify additional pathways.

Preterm birth and long-term maternal cardiovascular health.

PURPOSE To investigate whether preterm birth (PTB) is associated with greater cardiovascular disease (CVD) risk in a longitudinal cohort. METHODS We examined differences in systolic blood pressure (SBP), diastolic blood pressure, insulin resistance (Homeostatic model assessment of insulin resistance), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein, triglycerides, C-reactive protein, and interleukin 6 at 3 years postpartum between women who delivered preterm (gestation <37 weeks; n = 54) versus term (≥37 weeks; n = 751) using multivariable linear regression. We also assessed relations with body mass index, weight change from prepregnancy, and waist circumference at 3 and 7 years postpartum. RESULTS Median age at enrollment was 33.9 years (range: 16.4-44.9). After adjusting for age, race, prepregnancy body mass index, parity, marital status, education, and SBP during early pregnancy, women with PTB had 3.99 mm Hg (95% confidence interval, 0.82-7.16) higher SBP and 7.01 mg/dL (1.54-12.50) lower HDL than those who delivered at term. The association with SBP was attenuated after accounting for hypertension before or during pregnancy (2.78 mm Hg [-0.30 to 5.87]). PTB was not related to other postpartum outcomes. CONCLUSIONS PTB is related to greater CVD risk by 3 years postpartum as indicated by higher SBP and lower HDL. Although these associations may be due to preexisting conditions exacerbated during pregnancy, PTB may flag high-risk women for more vigilant CVD monitoring and lifestyle interventions.

Association of History of Gestational Diabetes With Long-term Cardiovascular Disease Risk in a Large Prospective Cohort of US Women

Importance Previous studies identify gestational diabetes (GD) as a risk factor for intermediate markers of cardiovascular disease (CVD) risk; however, few are prospective, evaluate hard CVD end points, or account for shared risk factors including body weight and lifestyle. Objective To prospectively evaluate history of GD in relation to incident CVD risk. Design, Setting, and Participants The Nurses’ Health Study II (NHS II) is an observational cohort study of US female nurses established in 1989, with ongoing follow-up. Biennial questionnaires updated behavioral characteristics, health outcomes, and lifestyle factors. Multivariable Cox models estimated the hazard ratio (HR) and 95% CI for CVD risk. We included 89 479 women who reported at least 1 pregnancy and were free of CVD and cancer at baseline. Follow-up through May 31, 2015, was complete for more than 90% of eligible participants. Exposures History of GD was self-reported at baseline (1989) via questionnaire and updated every 2 years. Main Outcomes and Measures We observed 1161 incident self-reported nonfatal or fatal myocardial infarction or stroke, confirmed via medical records. Results Participants had a mean (SD) age of 34.9 (4.7) years. Adjusting for age, prepregnancy body mass index, and other covariates, GD vs no GD was associated with subsequent CVD (HR, 1.43; 95% CI, 1.12-1.81). Additional adjustment for weight gain since pregnancy and updated lifestyle factors attenuated the association (HR, 1.29; 95% CI, 1.01-1.65). Classifying GD by progression to T2D in relation to CVD risk indicated a positive association for GD with progression to T2D vs no GD or T2D (HR, 4.02; 95% CI, 1.94-8.31), and an attenuated relationship for GD only (HR, 1.30; 95% CI, 0.99-1.71). Conclusions and Relevance Gestational diabetes was positively associated with CVD later in life, although the absolute rate of CVD in this younger cohort of predominantly white women was low. This relationship is possibly mediated in part by subsequent weight gain and lack of healthy lifestyle.

Pregnancy Complications as Markers for Subsequent Maternal Cardiovascular Disease: Validation of a Maternal Recall Questionnaire

BACKGROUND We designed and tested the validity of a questionnaire to characterize maternal recall of pregnancy complications associated with increased future cardiovascular disease risk, based on the 2011 American Heart Association (AHA) guidelines. METHODS A maternal recall questionnaire of pregnancy history was administered to 971 patients who had participated in a previous cohort study of 1,608 pregnant women. Medical records from the study pregnancy served as the gold standard. Prevalence, sensitivity (sens), specificity (spec), positive predictive value (PPV), negative predictive value (NPV), and/or Spearmans correlation coefficients (r) were calculated for each question. RESULTS A total of 526 (54%) individuals recontacted responded. Respondents were more likely to be older, white, educated, and nulliparous and were less likely to deliver low-birthweight infants in the study pregnancy than were individuals who did not respond. Mean length of recall was 4.35 years (standard deviation [SD] 0.46) postpartum. Maternal recall was most accurate for gestational diabetes (sens: 92%, spec: 98%, PPV: 79%, NPV: 99%), infant birthweight (r=0.95), and gestation length (r=0.85). Maternal recall was modest for preeclampsia (sens: 79%, spec: 97%, PPV: 68%, NPV: 98%) and pregnancy-associated hypertension, including preeclampsia or gestational hypertension (sens: 60%, spec: 95%, PPV: 64%, NPV: 94%). CONCLUSIONS This validation study demonstrated that the majority of women could accurately recall a history of gestational diabetes, infant birthweight, and gestational age at delivery, 4 years postpartum on average. Recall of preeclampsia and pregnancy-associated hypertension overall was modest. Maternal report of these pregnancy conditions may help clinicians identify women at increased risk for cardiovascular disease.

Lifestyle in progression from hypertensive disorders of pregnancy to chronic hypertension in Nurses’ Health Study II: observational cohort study

Objectives To study the association between lifestyle risk factors and chronic hypertension by history of hypertensive disorders of pregnancy (HDP: gestational hypertension and pre-eclampsia) and investigate the extent to which these risk factors modify the association between HDP and chronic hypertension. Design Prospective cohort study. Setting Nurses’ Health Study II (1991-2013). Participants 54 588 parous women aged 32 to 59 years with data on reproductive history and without previous chronic hypertension, stroke, or myocardial infarction. Main outcome measure Chronic hypertension diagnosed by a physician and indicated through nurse participant self report. Multivariable Cox proportional hazards models were used to investigate the development of chronic hypertension contingent on history of HDP and four lifestyle risk factors: post-pregnancy body mass index, physical activity, adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, and dietary sodium/potassium intake. Potential effect modification (interaction) between each lifestyle factor and previous HDP was evaluated with the relative excess risk due to interaction. Results 10% (n=5520) of women had a history of HDP at baseline. 13 971 cases of chronic hypertension occurred during 689 988 person years of follow-up. Being overweight or obese was the only lifestyle factor consistently associated with higher risk of chronic hypertension. Higher body mass index, in particular, also increased the risk of chronic hypertension associated with history of HDP (relative excess risk due to interaction P<0.01 for all age strata). For example, in women aged 40-49 years with previous HDP and obesity class I (body mass index 30.0-34.9), 25% (95% confidence interval 12% to 37%) of the risk of chronic hypertension was attributable to a potential effect of obesity that was specific to women with previous HDP. There was no clear evidence of effect modification by physical activity, DASH diet, or sodium/potassium intake on the association between HDP and chronic hypertension. Conclusion This study suggests that the risk of chronic hypertension after HDP might be markedly reduced by adherence to a beneficial lifestyle. Compared with women without a history of HDP, keeping a healthy weight seems to be especially important with such a history.

Process factors affecting door to percutaneous coronary intervention for acute myocardial infarction patients.

The purpose of this cross-sectional study was to identify key predictor variables with the most impact on door-to-balloon time for acute myocardial infarction patients. The authors examined arrival, process, and patient-related variables from retrospective data from calendar years 2006 and 2007 within a single community hospital (N = 273). The door-to-balloon time ranged from 28 to 167 minutes, with an average of 76.77 (standard deviation ±24.5) minutes. Key predictor variables identified through multivariate linear regression included portable chest X-ray, presentation from walk-in versus ambulance, responding cardiology group, emergency department (ED) time of arrival (day 8 am to 5 pm or night 5 pm to 8 am), ED day of arrival (weekday or weekend), if a code R was called prior to arrival, and if the patient was identified as having chest pain on admission to the ED. For patients with acute myocardial infarction at a single study site, the authors identified a number of key factors that delay prompt reperfusion.

Vitamin D supplementation and growth in urban Mongol school children: Results from two randomized clinical trials

Background Symptomatic vitamin D deficiency is associated with slowed growth in children. It is unknown whether vitamin D repletion in children with asymptomatic serum vitamin D deficiency can restore normal growth. Objective We tested the impact of vitamin D-supplementation on serum concentrations of 25-hydroxyvitamin D [25(OH)D] and short-term growth in Mongol children, with very low serum vitamin D levels in winter. Design We conducted two randomized, double-blind, placebo-controlled trials in urban school age children without clinical signs of rickets. The Supplementation Study was a 6-month intervention with an 800 IU vitamin D3 supplement daily, compared with placebo, in 113 children aged 12–15 years. A second study, the Fortification Study, was a 7-week intervention with 710 ml of whole milk fortified with 300 IU vitamin D3 daily, compared with unfortified milk, in 235 children aged 9–11 years. Results At winter baseline, children had low vitamin D levels, with a mean (±SD) serum 25-hydroxyvitamin D [25(OH)D] concentration of 7.3 (±3.9) ng/ml in the Supplementation Study and 7.5 (±3.8) ng/ml in the Fortification Study. The serum levels increased in both vitamin D groups—by 19.8 (±5.1) ng/ml in the Supplementation Study, and 19.7 (±6.1) ng/ml in the Fortification Study. Multivariable analysis showed a 0.9 (±0.3 SE) cm greater increase in height in the vitamin-D treated children, compared to placebo treated children, in the 6-month Supplementation Study (p = 0.003). Although the children in the 7-week Fortification Study intervention arm grew 0.2 (±0.1) cm more, on average, than placebo children this difference was not statistically significant (p = 0.2). There were no significant effects of vitamin D supplements on differences in changes in weight or body mass index in either trial. For the Fortification Study, girls gained more weight than boys while taking vitamin D 3 (p-value for interaction = 0.03), but sex was not an effect modifier of the relationship between vitamin D3 and change in either height or BMI in either trial. Conclusions Correcting vitamin D deficiency in children with very low serum vitamin D levels using 800 IU of vitamin D3 daily for six months increased growth, at least in the short-term, whereas, in a shorter trial of 300 IU of D fortified milk daily for 7 weeks did not.

Improving the postpartum care of women with a recent history of preeclampsia: a focus group study

ABSTRACT Objective: Women with prior preeclampsia are at increased risk of cardiovascular disease (CVD). This study investigated barriers and facilitators toward learning about this link and engaging in lifestyle modifications to reduce this risk. Methods: Four focus groups were held with 14 women within 6 months of a preeclamptic pregnancy. Results: Participants were unaware of the link between preeclampsia and CVD, suggested improvements to provider–patient communication, and discussed the benefits of social support and online tracking (weight, blood pressure) in making lifestyle modifications. Conclusions: Solutions offered may improve efforts to modify lifestyle and communication between providers and women about this link.