Elizabeth W. Triche

Hypertensive Pregnancy Disorders and Subsequent Cardiovascular Morbidity and Type 2 Diabetes Mellitus in the Mother

Minimal data exist concerning the relationship between hypertensive pregnancy disorders and various subsequent cardiovascular events and the effect of type 2 diabetes mellitus on these. In a registry-based cohort study, we identified women delivering in Denmark from 1978 to 2007 with a first singleton (n=782 287) and 2 first consecutive singleton deliveries (n=536 419). The exposures were gestational hypertension and mild and severe preeclampsia. We adjusted for preterm delivery, small for gestational age, placental abruption, and stillbirth and, in a second model, we also adjusted for the development of type 2 diabetes mellitus. The end points were subsequent hypertension, ischemic heart disease, congestive heart failure, thromboembolic event, stroke, and type 2 diabetes mellitus. The risk of subsequent hypertension was increased 5.31-fold (range: 4.90 to 5.75) after gestational hypertension, 3.61-fold (range: 3.43 to 3.80) after mild preeclampsia, and 6.07-fold (range: 5.45 to 6.77) after severe preeclampsia. The risk of subsequent type 2 diabetes mellitus was increased 3.12-fold (range: 2.63 to 3.70) after gestational hypertension and 3.68-fold (range: 3.04 to 4.46) after severe preeclampsia. Women having 2 pregnancies both complicated by preeclampsia had a 6.00-fold (range: 5.40 to 6.67) increased risk of subsequent hypertension compared with 2.70-fold (range: 2.51 to 2.90) for women having preeclampsia in their first pregnancy only and 4.34-fold (range: 3.98 to 4.74) for women having preeclampsia in their second pregnancy only. The risk of subsequent thromboembolism was 1.03-fold (range: 0.73 to 1.45), 1.53-fold (range: 1.32 to 1.77), and 1.91-fold (range: 1.35 to 2.70) increased after gestational hypertension and mild and severe preeclampsia, respectively. Thus, hypertensive pregnancy disorders are strongly associated with subsequent type 2 diabetes mellitus and hypertension, the latter independent of subsequent type 2 diabetes mellitus. The severity, parity, and recurrence of these hypertensive pregnancy disorders increase the risk of subsequent cardiovascular events.

Asthma symptoms, severity, and drug therapy: a prospective study of effects on 2205 pregnancies.

OBJECTIVE To prospectively examine in pregnant women whether asthma or asthma therapy influenced preterm delivery, intrauterine grown restriction (IUGR), or birthweight. METHODS We enrolled 873 pregnant women with a history of asthma, of whom 778 experienced asthma symptoms or took medication, and 1333 women with no asthma history, including 884 women with neither asthma diagnosis nor symptoms and 449 with symptoms but no diagnosis. Asthma symptoms, medication, and severity were classified according to 2002 Global Initiative for Asthma guidelines. RESULTS Preterm delivery was not associated with asthma diagnosis, severity, or symptoms but was associated with use of controller medications, independent of symptoms, specifically oral steroids and theophylline. Gestation was reduced by 2.22 weeks in women using oral steroids daily (P =.001) and 1.11 weeks after theophylline (P =.002). We observed a 24% (5-47%) increased risk for IUGR with each increased symptom step, which increased further in symptomatic women with no asthma diagnosis (31%, 4-65%) compared with women with neither asthma nor symptoms. CONCLUSIONS We found no effect of asthma symptoms or severity on preterm delivery but observed increased risks associated with use of oral steroid and theophylline. Intrauterine growth restriction was associated with asthma severity, which possibly reflects a hypoxic fetal effect. Women with asthma symptoms but no diagnosis were at particular risk of undermedication and delivering IUGR infants. These observations support guidelines that advocate active management of pregnant patients with mild or moderate asthma with beta(2) agonists, with oral steroids added only if severity increases. Symptomatic patients without an asthma diagnosis might need to be equally managed.

Improving Gait in Multiple Sclerosis Using Robot-Assisted, Body Weight Supported Treadmill Training:

Background. The majority of patients with multiple sclerosis (MS) develop progressive gait impairment, which can start early in the disease and worsen over a lifetime. A promising outpatient intervention to help improve gait function with potential for addressing this treatment gap is task-repetitive gait training. Methods. Body weight supported treadmill training (BWSTT) with or without robotic assistance (Lokomat) was tested using a randomized crossover design in 13 patients with relapsing-remitting, secondary progressive or primary progressive MS. Patients received 6 training sessions over 3 weeks of each intervention. Outcomes included changes in the timed 25-foot walk (T25FW), the 6-minute walk treadmill test (6MW) distance, the Kurtzke Expanded Disability Status Scale (EDSS), as well as double-limb support time and step length ratio. Results. There were no major differences in outcomes between treatment groups. The study population significantly improved on gait outcomes and the EDSS following BWSTT, including a 31% improvement in the T25FW, a 38.5% improvement in the 6MW, and a 1-point gain for the EDSS. Differences in pre/post changes were noted depending on gender, disease subtype, affected limb, and baseline EDSS. Conclusions. Although no differences in gait outcomes or the EDSS were found between treatment groups, this small pilot study of task-repetitive gait training resulted in significant within-subject improvements. BWSTT appears to be an activity-dependent intervention with potential to reduce gait impairment in MS.

Symptoms and Medication Use in Children with Asthma and Traffic-Related Sources of Fine Particle Pollution

Background Exposure to ambient fine particles [particulate matter ≤ 2.5 μm diameter (PM2.5)] is a potential factor in the exacerbation of asthma. National air quality particle standards consider total mass, not composition or sources, and may not protect against health impacts related to specific components. Objective We examined associations between daily exposure to fine particle components and sources, and symptoms and medication use in children with asthma. Methods Children with asthma (n = 149) 4–12 years of age were enrolled in a year-long study. We analyzed particle samples for trace elements (X-ray fluorescence) and elemental carbon (light reflectance). Using factor analysis/source apportionment, we identified particle sources (e.g., motor vehicle emissions) and quantified daily contributions. Symptoms and medication use were recorded on study diaries. Repeated measures logistic regression models examined associations between health outcomes and particle exposures as elemental concentrations and source contributions. Results More than half of mean PM2.5 was attributed to traffic-related sources motor vehicles (42%) and road dust (12%). Increased likelihood of symptoms and inhaler use was largest for 3-day averaged exposures to traffic-related sources or their elemental constituents and ranged from a 10% increased likelihood of wheeze for each 5-μg/m3 increase in particles from motor vehicles to a 28% increased likelihood of shortness of breath for increases in road dust. Neither the other sources identified nor PM2.5 alone was associated with increased health outcome risks. Conclusions Linking respiratory health effects to specific particle pollution composition or sources is critical to efforts to protect public health. We associated increased risk of symptoms and inhaler use in children with asthma with exposure to traffic-related fine particles.

Heterogeneity in assessing self-reports of caffeine exposure: Implications for studies of health effects

Background. Coffee and its metabolite caffeine are widely studied for their health effects but with inconclusive results. Caffeine is particularly difficult to assess, and therefore we explore heterogeneity of caffeine exposure. Methods. We categorized caffeine exposure among 2,478 pregnant women in southern New England during 1996–2000 by the traditional laboratory-based methods of M. Bunker and M. McWilliams. A subsample was examined to ascertain caffeine levels of brewed or purchased beverages actually consumed. Results. More than half (56.6%) of women drank coffee since becoming pregnant. Serving sizes ranged from 2 to 32 oz and are considerably larger than laboratory standards, which are typically 8–10 oz, as compared with the standard of 5 to 6 oz. Conversely, caffeine content per serving of coffee was one-third the laboratory standard, eg, 100 mg caffeine compared with 300 mg for a 10-oz cup. Tea brewed more than 3 minutes contained 42 mg caffeine as compared with the standard of 94 mg. When the amount of caffeine actually consumed was measured, one-quarter (24.8%) of subjects traditionally classified as consuming 300+ gm caffeine daily were reclassified as consuming 150–299 mg. Conclusion. Misclassification of caffeine consumption increases difficulty in identifying health effects from caffeine. Some combination of more precise consumption data and a biomarker such as paraxanthine may more precisely estimate exposure.

Clinical Characteristics of Children with Autism Spectrum Disorder and Co-Occurring Epilepsy

Objectives To estimate the prevalence of epilepsy in children with Autism Spectrum Disorder (ASD) and to determine the demographic and clinical characteristics of children with ASD and epilepsy in a large patient population. Methods Cross-sectional study using four samples of children with ASD for a total of 5,815 participants with ASD. The prevalence of epilepsy was estimated from a population-based sample. Children with and without epilepsy were compared on demographic and clinical characteristics. Multivariate logistic regression was used to examine the association between demographic and clinical characteristics and epilepsy. Results The average prevalence of epilepsy in children with ASD 2–17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy. Epilepsy was associated with older age, lower cognitive ability, poorer adaptive and language functioning, a history of developmental regression and more severe ASD symptoms. The association between epilepsy and the majority of these characteristics appears to be driven by the lower IQ of participants with epilepsy. In a multivariate regression model, only age and cognitive ability were independently associated with epilepsy. Children age 10 or older had 2.35 times the odds of being diagnosed with epilepsy (p<.001) and for a one standard deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001). Conclusion This is among the largest studies to date of patients with ASD and co-occurring epilepsy. Based on a representative sample of children with ASD, the average prevalence of epilepsy is approximately 12% and reaches 26% by adolescence. Independent associations were found between epilepsy and older age and lower cognitive ability. Other risk factors, such as poor language and developmental regression, are not associated with epilepsy after controlling for IQ. These findings can help guide prognosis and alert clinicians to patients with ASD who are at increased risk for epilepsy.

Association of pediatric asthma severity with exposure to common household dust allergens.

BACKGROUND Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. OBJECTIVE To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. METHODS Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mothers education. RESULTS Der p 1 house dust mite allergen concentration of 2.0 microg/g or more from the main room and the childs bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 microg/g and OR 2.55 95% CI 1.13, 5.73 for 10.0 microg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). CONCLUSION Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.

Association of asthma diagnosis, severity, symptoms, and treatment with risk of preeclampsia

OBJECTIVE: Existing studies relating asthma and preeclampsia provide conflicting results, perhaps due to differences in study populations, varying definitions of asthma, and inadequate control for confounding, particularly asthma medication use. This prospective study examines associations between aspects of asthma (diagnosis, severity, symptoms, and medication use) and risk of preeclampsia. METHODS: A total of 1,708 pregnant women, of whom 656 had asthma diagnosis and 1,052 had no asthma diagnosis, were included in this analysis. Asthma symptoms, treatment, and severity were classified according to Global Initiative for Asthma guidelines. Hospital records were abstracted, and strict criteria were applied to classify women as preeclamptic based on National Heart, Lung, and Blood Institute guidelines. RESULTS: There were 568 of 656 women with diagnosed asthma and 353 of 1,052 women without asthma diagnosis who had symptoms or took asthma medication during pregnancy. Separate adjusted logistic regression models were run for different measures of asthma status: 1) asthma diagnosis; 2) overall Global Initiative for Asthma severity; 3) Global Initiative for Asthma symptom and treatment steps; and 4) Global Initiative for Asthma symptom step and medication type. Women at increased risk of preeclampsia were those classified as Global Initiative for Asthma symptom step 3/4 compared with no symptoms (odds ratio 3.36, 95% confidence interval 1.24–9.14) and theophylline users (odds ratio 1.16 for every dose/month increase in use, 95% confidence interval 1.02–1.33). In contrast, neither a history of physician-diagnosed asthma nor Global Initiative for Asthma treatment step was associated with preeclampsia status. CONCLUSION: Our findings suggest that women with moderate to severe asthma symptoms, regardless of asthma diagnosis or treatment, are at increased risk of preeclampsia compared with women with no symptoms. LEVEL OF EVIDENCE: II-2

Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery

The combined effects of preterm delivery, small-for-gestational-age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy complications on early maternal death in a registry-based retrospective cohort study of 782 287 women with a first singleton delivery in Denmark 1978-2007, followed for a median of 14.8 years (range 0.25-30.2) accruing 11.6 million person-years. We employed Cox proportional hazard models of early death from cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non-cardiovascular causes. Severe pre-eclampsia was associated with death from cardiovascular causes only. There was a less than additive effect on cardiovascular mortality hazard ratios with increasing number of pregnancy complications: preterm delivery 1.90 [95% confidence intervals 1.49, 2.43]; preterm delivery and small-for-gestational-age offspring 3.30 [2.25, 4.84]; preterm delivery, small-for-gestational-age offspring and pre-eclampsia 3.85 [2.07, 7.19]. Thus, we conclude that, separately and combined, preterm delivery and small-for-gestational-age are strong markers of early maternal death from both cardiovascular and non-cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes.

Exposure to NO2 and nitrous acid and respiratory symptoms in the first year of life.

Background: Effects of nitrogen dioxide (NO2) on respiratory health have been the subject of extensive research. The outcomes of these studies were not consistent. Exposure to nitrous acid, which is a primary product of combustion, and is also formed when NO2 reacts with water, may play an important role in respiratory health. We estimate the independent effects of exposure to nitrogen dioxide and nitrous acid on respiratory symptoms during the first year of life. Methods: Nitrogen dioxide and nitrous acid concentrations were measured once (1996–1998) in the homes of 768 infants who were at risk for developing asthma. Infants were living in southern New England. The frequency of respiratory symptoms in these children was recorded during the first year of life. Results: Infants living in homes with an NO2 concentration exceeding 17.4 ppb (highest quartile) had a higher frequency of days with wheeze (rate ratio = 2.2; 95% confidence interval = 1.4–3.4), persistent cough (1.8; 1.2–2.7), and shortness of breath (3.1; 1.8–5.6) when compared with infants in homes that had NO2 concentrations lower than 5.1 ppb (lowest quartile), controlling for nitrous acid concentration. Nitrous acid exposure was not independently associated with respiratory symptoms. Conclusions: Among infants at risk for developing asthma, the frequency of reported respiratory symptoms in the first year of life was associated with levels of NO2 not currently considered to be harmful.