Diagnosis validation and clinical characterization of atopic dermatitis in Nurses' Health Study 2.

BACKGROUND: Epidemiologic studies of atopic dermatitis (AD) are often limited by case definitions that have not been validated. OBJECTIVE: In this study, we assessed the accuracy of self-report of AD in a large cohort of US female nurses, the Nurses' Health Study 2 (NHS2). We also provide clinical characteristics of AD in the cohort. METHODS: We sent an electronic questionnaire to NHS2 participants who previously reported ever having a diagnosis of AD. This questionnaire was designed to confirm cases of AD using previously validated algorithms with >85% specificity. We assessed the association of AD with asthma, comparing the results when different definitions of AD were applied. We also inquired about various aspects of participants' AD. RESULTS: Responses were received from 2509 of 5126 (49%) nurses who were sent the questionnaire, with an average age of 62. Most participants (1996/2509, 80%) reiterated their previously reported clinician diagnosis of AD. Application of the two diagnostic algorithms yielded confirmation of 1538 and 1293 prevalent cases, respectively. The association of AD with asthma was stronger when more stringent AD case definitions were applied. Participants generally reported mild disease (92% with ≤10% maximal body surface area involved) and a high proportion (57%) reported adult-onset disease. CONCLUSIONS: Self-report of AD diagnosis has good reliability, and future analyses will be strengthened by our ability to conduct sensitivity analyses with refined confirmed AD subgroups.

Circulating 25-hydroxyvitamin D, nasopharyngeal airway metabolome, and bronchiolitis severity.

Low circulating 25-hydroxyvitamin D (25OHD) levels are a risk factor for acute respiratory infection (eg, bronchiolitis) in children. However, little is known about the relation of circulating 25OHD with the many downstream functional molecules in target organs-such as the airway-and with clinical outcomes. In this prospective multicenter study of infants (age <1 year) hospitalized with bronchiolitis, we measured serum 25OHD levels and profiled the metabolome of 144 nasopharyngeal airway samples. Among 254 metabolites identified, we defined a set of 20 metabolites that are related to lower serum 25OHD and higher vitamin D-binding protein levels. Of these metabolites, 9 metabolites were associated with a significantly higher risk of positive pressure ventilation use. These metabolites were glycerophosphocholines esterified with proinflammatory fatty acids (palmitate, arachidonate, linoleate, and stearate), sphingomyelins, alpha-hydroxyisovalerate, 2-hydroxybutyrate, and 3-(4-hydroxyphenyl)lactate (all FDR<0.05). Based on the multicenter data, vitamin D-related airway metabolites were associated with risks of bronchiolitis severity.

Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression.

BACKGROUND: The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression. METHODS: Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS. RESULTS: Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38]). CONCLUSION: While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.

Immunohistochemical expression of vitamin D receptor in melanocytic naevi and cutaneous melanoma: a case-control study.

BACKGROUND: Vitamin D deficiency is associated with higher risk of cancer, possibly due to its antiproliferative, antiangiogenic, proapoptotic, cell-differentiating and anti-invasive effects. The anticarcinogenic role of vitamin D in melanoma is still a matter of debate. Loss of nuclear and cytoplasmic vitamin D receptor (VDR) expression in melanoma cells has been reported. OBJECTIVES: To analyse VDR immunohistochemical expression in benign dermal naevi (DN) and malignant melanoma (MM). METHODS: A case-control study evaluated nuclear and cytoplasmic VDR immunohistochemical staining in 54 DN and 55 MM tissue samples. RESULTS: There was significantly higher cytoplasmic VDR positivity in DN compared with MM (59% vs. 16%, P < 0·001). The mean VDR cytoplasmic expression was also higher in DN vs. MM (P < 0·001). No differences in nuclear VDR positivity were observed between groups, but mean nuclear VDR expression was significantly lower in DN vs. MM (P = 0·02). The loss of cytoplasmic VDR in MM was associated with Clark level, tumour staging and American Joint Committee on Cancer pTNM staging (P=0·004, 0·009 and 0·02, respectively). CONCLUSIONS: Alterations in VDR expression and localization are found in MM compared with DN. Loss of cytoplasmic VDR was associated with melanoma tumour size, suggesting that loss of cytoplasmic VDR may be a prognostic factor.

Effect of monthly high-dose vitamin D on bone density in community-dwelling older adults substudy of a randomized controlled trial.

BACKGROUND: Severe vitamin D deficiency causes osteomalacia, yet trials of vitamin D supplementation in the community have not on average demonstrated benefit to bone mineral density (BMD) or fracture risk in adults. OBJECTIVE: To determine whether monthly high-dose vitamin D supplementation influences BMD in the general population and in those with low 25-hydroxyvitamin D levels. METHODS: Two-year substudy of a trial in older community-resident adults. A total of 452 participants were randomized to receive monthly doses of vitamin D3 100 000 IU, or placebo. The primary end-point was change in lumbar spine BMD. Exploratory analyses to identify thresholds of baseline 25-hydroxyvitamin D for vitamin D effects on BMD were prespecified. RESULTS: Intention-to-treat analyses showed no significant treatment effect in the lumbar spine (between-groups difference 0.0071 g cm-2 , 95%CI: -0.0012, 0.0154) or total body but BMD loss at both hip sites was significantly attenuated by ~1/2% over 2 years. There was a significant interaction between baseline 25-hydroxyvitamin D and treatment effect (P = 0.04). With baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 (n = 46), there were between-groups BMD changes at the spine and femoral sites of ~2%, significant in the spine and femoral neck, but there was no effect on total body BMD. When baseline 25-hydroxyvitamin D was >30 nmol L-1 , differences were ~1/2% and significant only at the total hip. CONCLUSIONS: This substudy finds no clinically important benefit to BMD from untargeted vitamin D supplementation of older, community-dwelling adults. Exploratory analyses suggest meaningful benefit in those with baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 . This represents a significant step towards a trial-based definition of vitamin D deficiency for bone health in older adults.

Celiac disease is associated with reduced bone mineral density and increased FRAX scores in the US National Health and Nutrition Examination Survey.

We investigated the association between celiac disease (CD) and bone mass density (BMD) and risk of osteoporotic fractures in the general US population. In children and men ≥18 years, CD was associated with reduced BMD, and in men ≥40 years, CD was associated with increased risk of osteoporotic fractures. INTRODUCTION: Celiac disease (CD) is an autoimmune condition, characterized by inflammation of the small intestine. CD has an increasing prevalence, and if unrecognized or untreated, CD can lead to complications from malabsorption and micronutrient deficiencies. We aimed to study whether CD is an independent predictor of reduced bone mineral density (BMD) and FRAX scores in the general US population. METHODS: We used data from the National Health and Nutrition Examination Survey, 2009-2010 and 2013-2014. CD was defined by positive tissue transglutaminase IgA antibody test. Multivariable models of BMD and FRAX scores were adjusted for BMI, serum 25-hydroxyvitamin D, vitamin D and calcium supplements, milk intake, serum calcium, and smoking status, when available. RESULTS: In children, aged 8-17 years, CD was associated with decreased Z-scores, by 0.85 for hip and 0.46 for spine (both P < 0.001). In men aged ≥ 18 years, CD was associated with 0.06 g/cm2 decrease in BMD in hip and with 0.11 g/cm2 decrease in BMD in spine (P = 0.08 and P < 0.001, respectively). In women, there were no statistically significant differences in the multiple-adjusted model. In men aged ≥ 40 years, CD predicted FRAX scores, resulting in increased scores by 2.25 % (P = 0.006) for hip fracture and by 2.43 % (P = 0.05) for major osteoporotic fracture. CD did not predict FRAX scores in women aged ≥40 years. CONCLUSION: CD is independently associated with reduced BMD in children and adults aged ≥18 years and is an independent risk factor of osteoporotic fractures in men aged ≥40 years.

The relationship between nasopharyngeal CCL5 and microbiota on disease severity among infants with bronchiolitis.

Emerging evidence suggests that the airway microbiota plays an important role in viral bronchiolitis pathobiology. However, little is known about the combined role of airway microbiota and CCL5 in infants with bronchiolitis. In this multicenter prospective cohort study of 1005 infants (age <1 year) hospitalized for bronchiolitis during 2011-2014, we observed statistically significant interactions between nasopharyngeal airway CCL5 levels and microbiota profiles with regard to the risk of both intensive care use (Pinteraction =.02) and hospital length-of-stay ≥3 days (Pinteraction =.03). Among infants with lower CCL5 levels, the Haemophilus-dominant microbiota profile was associated with a higher risk of intensive care use (OR, 3.20; 95%CI, 1.18-8.68; P=.02) and hospital length-of-stay ≥3 days (OR, 4.14; 95%CI, 2.08-8.24; P<.001) compared to the Moraxella-dominant profile. Conversely, among those with higher CCL5 levels, there were no significant associations between the microbiota profiles and these severity outcomes (all P≥.10).

Regional solar radiation is inversely correlated with incidence and severity of tuberculosis in Chile.

Vitamin D (VD) deficiency has been linked to increased incidence and morbidity of tuberculosis (TB). Chile has large variations in solar radiation (SR; a proxy of VD status) and high prevalence of VD deficiency in its southernmost regions with low SR. We investigated the correlation between regional SR and rates of TB incidence, admissions and deaths in Chile by reviewing national records on prospectively collected mandatory disease notifications, admissions and mortality between 2001 and 2011. Over the study period, 26 691 new TB notifications were registered. The TB incidence rate was 14·77 (95% confidence intervals (CIs) 14·60-14·95), admission rate was 12·12 (95% CI 11·96-12·28) and mortality rate was 1·61 (95% CI 1·55-1·67) per 100 000 population per year. Multivariable linear regressions adjusting for significant demographic TB risk factors in Chile (regional prevalence of HIV infection, rates of migration from TB-endemic countries and rates of imprisonment) revealed an independent and highly statistically significant inverse association between SR and TB incidence rate (ß -1·05, 95% CI -1·73 to -0·36, P = 0·007), admission rate (ß -1·58, 95% CI -2·23 to -0·93, P < 0·001), and mortality rate (ß -0·15, 95% CI -0·23 to -0·07, P = 0·002). These findings support a potential pathogenic role of VD deficiency in TB incidence and severity.

Development of a job-task-exposure matrix to assess occupational exposure to disinfectants among US nurses.

OBJECTIVES: Occupational exposure to disinfectants is associated with work-related asthma, especially in healthcare workers. However, little is known about the specific products involved. To evaluate disinfectant exposures, we designed job-exposure (JEM) and job-task-exposure (JTEM) matrices, which are thought to be less prone to differential misclassification bias than self-reported exposure. We then compared the three assessment methods: self-reported exposure, JEM and JTEM. METHODS: Disinfectant use was assessed by an occupational questionnaire in 9073 US female registered nurses without asthma, aged 49-68 years, drawn from the Nurses' Health Study II. A JEM was created based on self-reported frequency of use (1-3, 4-7 days/week) of 7 disinfectants and sprays in 8 nursing jobs. We then created a JTEM combining jobs and disinfection tasks to further reduce misclassification. Exposure was evaluated in 3 classes (low, medium, high) using product-specific cut-offs (eg, <30%, 30-49.9%, ≥50%, respectively, for alcohol); the cut-offs were defined from the distribution of self-reported exposure per job/task. RESULTS: The most frequently reported disinfectants were alcohol (weekly use: 39%), bleach (22%) and sprays (20%). More nurses were classified as highly exposed by JTEM (alcohol 41%, sprays 41%, bleach 34%) than by JEM (21%, 30%, 26%, respectively). Agreement between JEM and JTEM was fair-to-moderate (κ 0.3-0.5) for most disinfectants. JEM and JTEM exposure estimates were heterogeneous in most nursing jobs, except in emergency room and education/administration. CONCLUSIONS: The JTEM may provide more accurate estimates than the JEM, especially for nursing jobs with heterogeneous tasks. Use of the JTEM is likely to reduce exposure misclassification.

Predictors of vitamin D status in New Zealand preschool children.

Vitamin D deficiency has adverse health effects in young children. Our aims were to determine predictors of vitamin D status and then to use these factors to develop a practical tool to predict low 25(OH)D concentrations in preschool New Zealand children. A cross-sectional sample of 1329 children aged 2 to <5 years were enrolled from throughout New Zealand in late-winter to spring 2012. 25-Hydroxyvitamin D (25(OH)D) was measured on dried blood spot (DBS) samples collected using finger-prick sampling. Caregivers completed a questionnaire. Mean (SD) DBS 25(OH)D concentration was 52(19)nmol/L. 25(OH)D < 25 nmol/L was present in 86(7%), 25(OH)D < 50 nmol/L in 642(48%), 25(OH)D 50- < 75 nmol/L in 541(41%) and 25(OH)D > 75 nmol/L in 146(11%) of children. Factors independently associated with the risk of 25(OH)D < 25 nmol/L were female gender (OR 1.92,95%CI 1.17-3.14), other non-European ethnicities (not including Maori or Pacific) (3.51,1.89-6.50), had olive-dark skin colour (4.52,2.22-9.16), did not take vitamin D supplements (2.56,1.06-6.18), had mothers with less than secondary-school qualifications (5.00,2.44-10.21) and lived in more deprived households (1.27,1.06-1.53). Children who drank toddler milk (vitamin D fortified cow's milk formula marketed to young children) had a zero risk of 25(OH)D < 25 nmol/L. The predictive tool identified children at risk of 25(OH)D < 25 nmol/L with sensitivity 42%, specificity 97% and ROC area-under-curve 0.76(95%CI 0.67-0.86, p < 0.001). Predictors of low vitamin D status were consistent with those identified in previous studies of New Zealand children. The tool had insufficient predictive ability for use in clinical situations, and suggests a need to promote safe, inexpensive testing to determine vitamin D status in preschool children.

Longitudinal study of maternal body mass index, gestational weight gain, and offspring asthma.

BACKGROUND: Sparse data are available on the relationship between prenatal exposures and asthma during later childhood. In a longitudinal study of adolescents and their mothers, we examined the association of (i) maternal prepregnancy body mass index (BMI) and (ii) gestational weight gain (GWG), with incidence of allergic and nonallergic asthma in offspring. METHODS: Analyses were conducted using data from 12 963 children aged 9-14 years at enrolment in the Growing Up Today Study, and their mothers, who are participants in the Nurses' Health Study II. Physician-diagnosed asthma and allergies were assessed by questionnaires sent regularly to participants and their mothers. Logistic regression was used to evaluate associations of maternal BMI and GWG with offspring asthma, overall and by subtype. RESULTS: Physician-diagnosed asthma during childhood or adolescence was reported by 2694 children (21%). Maternal prepregnancy overweight (OR: 1.19, 95% CI: 1.03-1.38) and obesity (1.34, 1.08-1.68) were associated with offspring asthma. In asthma subtype analyses, the association was seen only for asthma onset before age 12 years. Moreover, the association of maternal obesity with nonallergic asthma was observed in boys (2.39, 1.40-4.09) and not in girls (0.96, 0.50-1.85; Pinteraction = 0.03); the opposite pattern was suggested for allergic asthma. With regard to GWG, an association was suggested between gains of <15 lb and higher risk of offspring asthma (1.28, 0.98-1.66), without clear allergy- or sex-related patterns. CONCLUSION: The relation of several prenatal factors to risk of childhood asthma supports the early origins hypothesis for asthma. The observed allergy- and sex-specific patterns suggest multiple etiologic pathways.

Atopic dermatitis is not independently associated with nonfatal myocardial infarction or stroke among US women.

We aimed to determine the association between atopic dermatitis (AD) and cardiovascular events in the Nurses' Health Study 2, a cohort of US women. We used logistic regression models to calculate age- and multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between history of AD and nonfatal MI and nonfatal stroke. Of the 78 702 participants in our analysis, 7916 (10%) had a history of AD. There were 392 and 391 cases of nonfatal MI and stroke, respectively. AD was not associated with MI in age- or multivariate-adjusted analyses. AD was significantly associated with stroke in the age-adjusted analysis (OR 1.38, 95% CI 1.03-1.85). This was no longer significant in multivariate models that adjusted for hypertension, hypercholesterolemia and diabetes (OR 1.31, 95% CI 0.98-1.76) and atopic comorbidities (OR 1.17, 95% CI 0.86-1.58). AD was not independently associated with nonfatal MI or stroke in this study.

Vitamin D supplementation during pregnancy and infancy reduces aeroallergen sensitization: a randomized controlled trial.

BACKGROUND: Vitamin D has immune-modulating effects. We determined whether vitamin D supplementation during pregnancy and infancy prevents aeroallergen sensitization and primary care respiratory illness presentations. METHODS: A randomized, double-blind, placebo-controlled parallel-group trial. We assigned pregnant women, from 27-week gestation to birth, and then their infants, from birth to 6 months, to placebo or one of two dosages of daily oral vitamin D. Woman/infant pairs were randomized to: placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. When the children were 18 months old, we measured serum-specific IgE antibodies and identified acute primary care visits described by the doctor to be due to a cold, otitis media, an upper respiratory infection, croup, asthma, bronchitis, bronchiolitis, a wheezy lower respiratory infection or fever and cough. RESULTS: Specific IgE was measured on 185 of 260 (71%) enrolled children. The proportion of children sensitized differed by study group for four mite antigens: Dermatophagoides farinae (Der-f1, Der-f2) and Dermatophagoides pteronyssinus (Der-p1, Der-p2). With results presented for placebo, lower dose, and higher dose vitamin D, respectively (all P < 0.05): Der-f1 (18%, 10%, 2%), Der-f2 (14%, 3%, 2%), Der-p1 (19%, 14%, 3%) and Der-p2 (12%, 2%, 3%). There were study group differences in the proportion of children with primary care visits described by the doctor as being for asthma (11%, 0%, 4%, P = 0.002), but not for the other respiratory diagnoses. CONCLUSIONS: Vitamin D supplementation during pregnancy and infancy reduces the proportion of children sensitized to mites at age 18 months. Preliminary data indicate a possible effect on primary care visits where asthma is diagnosed.

Serum 25-hydroxyvitamin D levels and self-reported allergic rhinitis in Norwegian adults - The HUNT Study.

BACKGROUND: The role of low vitamin D status in the development of allergic rhinitis is unclear. We aimed to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] and incidence of allergic rhinitis in adults. METHODS: The study included a random sample from an adult population who participated in the second and third surveys of the Nord-Trøndelag Health Study (HUNT) in Norway (HUNT2, 1995-1997 and HUNT3, 2006-2008). Serum 25(OH)D levels were measured in blood samples collected at baseline. Among 1351 adults who did not report allergic rhinitis at baseline, incident allergic rhinitis was identified by participant report of having or having had allergic rhinitis or hay fever at follow-up. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated after adjustment for age, smoking, physical activity, socioeconomic status, family history of allergy, body mass index, and season. The analyses were stratified by sex due to its significant interaction with 25(OH)D levels (P < 0.02). RESULTS: Over an average of 11 years, 9% of men and 15% of women developed allergic rhinitis. Among men, serum 25(OH)D level <50 nM was associated with an increased risk of incident allergic rhinitis (AOR 2.55; 95% CI 1.01-6.49); each 25 nM reduction in 25(OH)D level was associated with an AOR of 1.84 (95% CI 1.18-2.87). In women, however, the association was opposite, with AOR being 0.83 (95% CI 0.66-1.05) for each 25 nM reduction in serum 25(OH)D level. CONCLUSIONS: Vitamin D appears to play different roles in the development of allergic rhinitis among men and women.

The effects of the DASH dietary pattern on clinical outcomes and quality of life in adults with uncontrolled asthma: Design and methods of the ALOHA Trial.

BACKGROUND: Poor diet quality is an important risk factor for increased asthma prevalence and poor asthma control. To address the question of whether adults with asthma can benefit from following a healthy diet, this trial will test the efficacy and mechanisms of action of a behavioral intervention promoting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern with sodium reduction among patients with uncontrolled asthma. METHODS: In this 2-arm randomized clinical trial, 320 racially/ethnically and socioeconomically diverse adults with uncontrolled asthma on standard controller therapy will be randomized to either a control or an intervention group and assessed at baseline, 3, 6 and 12 months. Control and intervention participants will receive education on lung health, asthma, and other general health topics; additionally, the intervention group will receive DASH behavioral counseling over 12 months. The primary hypothesis is that the DASH behavioral intervention, compared with the education-only control, will lead to significantly more participants with minimum clinically important improvement (responders) in asthma-specific quality of life at 12 months. Secondary hypotheses will test the intervention effects on other asthma (e.g., asthma control, lung function) and non-asthma outcomes (e.g., quality of life). Additionally, therapeutic (e.g., short chain fatty acids, cytokines) and nutritional biomarkers (e.g., dietary inflammatory index, carotenoids) will be assessed to understand the mechanisms of the intervention effect. CONCLUSION: This trial can substantially advance asthma care by providing rigorous evidence on the benefits of a behavioral dietary intervention and mechanistic insights into the role of diet quality in asthma. CLINICALTRIALS: gov #: NCT05251402.

Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women.

OBJECTIVE: To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. DESIGN: A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. SETTING: Fourteen academic health centres in the USA. POPULATION: Women with prior spontaneous preterm birth. METHODS: In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. MAIN OUTCOME MEASURES: Recurrent preterm birth at <37 and <32 weeks of gestation. RESULTS: The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). CONCLUSIONS: In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.

Defining vitamin D status by secondary hyperparathyroidism in the U.S. population.

BACKGROUND: Vitamin D is associated with a variety of health outcomes, but the exact definition of vitamin D sufficiency remains controversial. AIM: We sought to define skeletal-related vitamin D sufficiency by estimating maximum PTH suppression in the U.S. population. METHODS: We performed a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES), 2003-2006. We examined the association between serum 25-hydroxyvitamin D (25OHD) level and serum PTH level in 14,681 participants aged ≥6 yr. We also evaluated the 25OHD-PTH association using 2 thresholds of hyperparathyroidism: PTH≥45 pg/ml and ≥75 pg/ml. RESULTS: The mean 25OHD level was 24 ng/ml and mean PTH was 42 pg/ml. PTH≥45 pg/ml was present in 35% of the population, while PTH≥75 pg/ml was present in 7%. The prevalence of 25OHD levels <40 ng/ml and <30 ng/ml was 95% and 77%, respectively. In both unadjusted and adjusted models, there was a strong inverse relationship between 25OHD and PTH. Compared to 25OHD≥40 ng/ml, the 25OHD-PTH association was 2.36 [95% confidence interval (CI), 2.08-2.67] times greater for 25OHD<5 ng/ml and 1.12 (95%CI, 1.07-1.17) times greater for 25OHD 30-39.9 ng/ml. Compared to 25OHD≥40 ng/ml, 25OHD levels of 20- 29.9 ng/ml [odds ratio (OR) 2.0 (95%CI, 1.4-2.8)] but not 30- 39.9 ng/ml [OR 1.1 (95%CI, 0.8-1.6)] were independently associated with PTH≥45 pg/ml. CONCLUSIONS: Optimal vitamin D status, defined by estimated maximum PTH suppression, does not occur until at least 25OHD levels ≥40 ng/ml. Using these thresholds, most of the U.S. population needs more vitamin D. Large, prospective studies are needed to determine optimal vitamin D supplementation.