Sara S. Oberhelman

Maternal vitamin D supplementation to improve the vitamin D status of breast-fed infants: A randomized controlled trial

OBJECTIVE To determine whether a single monthly supplement is as effective as a daily maternal supplement in increasing breast milk vitamin D to achieve vitamin D sufficiency in their infants. PATIENTS AND METHODS Forty mothers with exclusively breast-fed infants were randomized to receive oral cholecalciferol (vitamin D3) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum, breast milk, and urine were collected on days 0, 1, 3, 7, 14, and 28; infant serum was obtained on days 0 and 28. Enrollment occurred between January 7, 2011, and July 29, 2011. RESULTS In mothers given daily cholecalciferol, concentrations of serum and breast milk cholecalciferol attained steady levels of 18 and 8 ng/mL, respectively, from day 3 through 28. In mothers given the single dose, serum and breast milk cholecalciferol peaked at 160 and 40 ng/mL, respectively, at day 1 before rapidly declining. Maternal milk and serum cholecalciferol concentrations were related (r=0.87). Infant mean serum 25-hydroxyvitamin D concentration increased from 17±13 to 39±6 ng/mL in the single-dose group and from 16±12 to 39±12 ng/mL in the daily-dose group (P=.88). All infants achieved serum 25-hydroxyvitamin D concentrations of more than 20 ng/mL. CONCLUSION Either single-dose or daily-dose cholecalciferol supplementation of mothers provided breast milk concentrations that result in vitamin D sufficiency in breast-fed infants. CLINICAL TRIAL REGISTRATION clinicaltrials.gov NCT01240265.

Changing Incidence of Serum 25-Hydroxyvitamin D Values Above 50 ng/mL: A 10-Year Population-Based Study

OBJECTIVE To determine the incidence trend of 25-hydroxyvitamin D (25(OH)D) values above 50 ng/mL and associated toxicity. PATIENTS AND METHODS We conducted a retrospective population-based study in Olmsted County, Minnesota, in the 10-year period from January 1, 2002, through December 31, 2011, by using the Rochester Epidemiology Project. Individuals were eligible if they resided in Olmsted County during the study period and had a measured 25(OH)D value above 50 ng/mL. The date of the first 25(OH)D value above 50 ng/mL was considered the index date for incidence determination. Hypercalcemia, the primary vitamin D toxicity, was considered potentially associated with the 25(OH)D concentration if it was measured within 3 months of the 25(OH)D measurement, and such cases had a medical record review. RESULTS Of 20,308 total 25(OH)D measurements, 1714 (8.4%), 123 (0.6%), and 37 (0.2%) unique persons had 25(OH)D values above 50, 80 and above, and 100 ng/mL and above, respectively. The age- and sex-adjusted incidence of 25(OH)D values above 50 ng/mL increased from 9 to 233 cases per 100,000 person-years from 2002 to 2011 (P<.001), respectively, and was greatest in persons aged 65 years and older (P<.001) and in women (P<.001). Serum 25(OH)D values were not significantly related to serum calcium values (P=.20) or with the risk of hypercalcemia (P=.24). A medical record review identified 4 cases (0.2%) in whom 25(OH)D values above 50 ng/mL were temporally associated with hypercalcemia, but only 1 case had clinical toxicity associated with the highest observed 25(OH)D value of 364 ng/mL. CONCLUSION The incidence of 25(OH)D values above 50 ng/mL increased significantly between 2002 and 2011 without a corresponding increase in acute clinical toxicity.

Maternal Preferences for Vitamin D Supplementation in Breastfed Infants

Daily vitamin D supplementation is recommended for breastfed infants, but alternative methods include enriching breast milk with vitamin D through maternal supplementation or intermittent high-dose vitamin D. We determined maternal preferences for vitamin D supplementation in 140 mothers with exclusively breastfed infants, and 44 who used both breast and formula milk. Only 101 (55%) supplemented their infants with vitamin D. One hundred sixty (88%) preferred supplementing themselves rather than their infants, and 102 (57%) preferred daily to monthly supplementation. Safety was most important in choosing a method of supplementation. Taking maternal preferences into consideration may improve adequate intakes of vitamin D in breastfed infants.

Pharmacokinetics of daily versus monthly vitamin D3 supplementation in non-lactating women.

This study compared serum cholecalciferol and 25-hydroxyvitamin D (25(OH)D) concentrations over four weeks in healthy, non-pregnant, non-lactating females aged 18–40 years, who were randomized to oral cholecalciferol 5000 international units (IU) daily for 28 days or a single dose of 150 000 IU. The study was conducted in Rochester, MN in March and April of 2010. We found no difference in mean 25(OH)D between treatment groups on study day 0 or day 28 (P=0.14 and 0.28, respectively). The daily group had 11 more days of detectable serum cholecalciferol than the single-dose group (P<0.001). There was no difference observed in cholecalciferol area under the curve (AUC28) between groups (P=0.49). However, the single-dose group had a significantly greater mean 25(OH)D AUC28 compared with the daily group (P<0.001).

Screening For Hypertension Annually Compared With Current Practice

PURPOSE Hypertension is the most common diagnosis in ambulatory care, yet little evidence exists regarding recommended screening intervals or the sensitivity and specificity of a routine office-based blood pressure measurement, the most common screening test. Screening for hypertension is usually performed by measuring blood pressure at every outpatient visit, which often results in transiently elevated findings among adults who do not have a diagnosis of hypertension. We hypothesize that a more limited annual screening strategy may increase specificity while maintaining sensitivity. METHODS A retrospective case-control study of 372 adults without hypertension and 68 patients with newly diagnosed hypertension was conducted to compare the usual screening practice of checking blood pressure at every visit with a second strategy that considered only annual blood pressure measurements. RESULTS Specificity improved from 70.4% (95% CI, 65.5%-75.0%) for the usual practice to 82.0% (95% CI, 77.7%-85.8%) for the annual screening strategy. No statistically significant difference in sensitivity existed between the 2 methods. CONCLUSION A limited annual screening strategy for hypertension can improve specificity without sacrificing sensitivity when compared with routine screening at every visit in previously normotensive adults.

Diabetes and Obesity Not Associated With 6-Month Remission Rates for Primary Care Patients With Depression

BACKGROUND Complex interrelationships appear to exist among depression, diabetes, and obesity, and it has been proposed that both diabetes and obesity have an association with depression. OBJECTIVE The purpose of our study was to explore the effect of obesity and diabetes on response to the treatment of depression. Our hypothesis was that obesity and the diagnosis of diabetes in primary care patients with depression would have no effects on depression remission rates 6 months after diagnosis. METHODS A retrospective chart review analysis of 1894 adult (age ≥18y) primary care patients diagnosed with major depressive disorder or dysthymia and a Patient Health Questionnaire-9 score ≥10 from January 1, 2008, through September 30, 2012. Multiple logistic regression modeling retaining all independent variables was performed for the outcome of remission (Patient Health Questionnaire-9 < 5) 6 months after diagnosis. RESULTS The presence of obesity (odds ratio = 0.937, 95% CI: 0.770-1.140, p = 0.514) or the diagnosis of diabetes (odds ratio = 0.740, 95% CI: 0.535-1.022, p = 0.068) did not affect the likelihood of remission, while controlling for the other independent variables. CONCLUSIONS In primary care patients treated for depression, the presence of diabetes or obesity at the time of diagnosis of depression does not appear to significantly affect remission of depressive symptoms 6 months after diagnosis.

Impact of symptom remission on outpatient visits in depressed primary care patients treated with collaborative care management and usual care.

Depression symptoms contribute to significant morbidity and health care utilization. The aim of this study was to determine the impact of symptom improvement (to remission) on outpatient clinical visits by depressed primary care patients. This study was a retrospective chart review analysis of 1733 primary care patients enrolled into collaborative care management (CCM) or usual care (UC) with 6-month follow-up data. Baseline data (including demographic information, clinical diagnosis, and depression severity) and 6-month follow-up data (Patient Health Questionnaire scores and the number of outpatient visits utilized) were included in the data set. To control for individual patient complexity and pattern of usage, the number of outpatient visits for 6 months prior to enrollment also was measured as was the presence of medical comorbidities. Multiple logistic regression analysis demonstrated that clinical remission at 6 months was an independent predictor of outpatient visit outlier status (>8 visits) (odds ratio [OR] 0.609, confidence interval (CI) 0.460-0.805, P<0.01) when controlling for all other independent variables including enrollment into CCM or UC. The OR of those patients not in remission at 6 months having outpatient visit outlier status was the inverse of this at 1.643 (CI 1.243-2.173). The most predictive variable for determining increased outpatient visit counts after diagnosis of depression was increased outpatient visits prior to diagnosis (OR 4.892, CI 3.655-6.548, P<0.01). In primary care patients treated for depression, successful treatment to remission at 6 months decreased the likelihood of the patient having more than 8 visits during the 6 months after diagnosis.

Timely response to secure messages from primary care patients.

Purpose: To assess delays in response to patient secure e-mail messages in primary care. Background: Secure electronic messages are initiated by primary care patients. Timely response is necessary for patient safety and quality. Data Source: A database of secure messages. Sample: A random sample of 353 secure electronic messages initiated by primary care patients treated in 4 clinics. Outcome Measures: Message not opened after 12 hours or messages not responded to after 36 hours. Results: A total of 8.5% of electronic messages were not opened within 12 hours, and 17.6% did not receive a response in 36 hours. Clinic location, being a clinic employee, and patient sex were not related to delays. Patients older than 50 years were more likely to receive a delayed response (25.7% delayed, P = .013). The risk of both kinds of delays was higher on weekends (P < .001 for both). Conclusion: The e-mail message system resulted in high rates of delayed response. Delays were concentrated on weekends (Friday-Sunday). Reducing delayed responses may require automatic rerouting of messages to message centers staffed 24–7 or other mechanisms to manage this after-hours work flow.

Vitamin D and the Breastfeeding Infant: Family Medicine Clinicians’ Knowledge, Attitudes, and Practices:

Background: The American Academy of Pediatrics and the National Academy of Medicine recommend vitamin D supplementation for breastfeeding infants. However, compliance with this recommendation is poor. Maternal supplementation with vitamin D is a safe and effective alternative to achieving vitamin D sufficiency in breastfeeding infants, and mothers have indicated a preference for self-supplementation over infant supplementation. Research aim: We sought to explore Family Medicine clinicians’ knowledge, attitudes, and practices regarding vitamin D supplementation recommendations for breastfeeding dyads. Methods: Fifty-six Family Medicine clinicians (including faculty physicians, resident physicians, and nurse practitioners/physician assistants) completed an online, anonymous survey regarding their knowledge and practices concerning vitamin D supplementation for breastfeeding infants. Results: The vast majority of clinicians (92.9%) correctly identified the American Academy of Pediatrics’ 2008 recommended dose for vitamin D supplementation in breastfeeding infants and estimated recommending vitamin D supplementation of exclusively breastfeeding infants 70.1% of the time. If all options were equivalent, clinicians would prefer to offer maternal or infant supplementation (50%) or maternal supplementation (37.5%) over infant supplementation (12.5%). Most (69.6%) preferred daily over monthly supplementation regimens. Conclusion: Family Medicine clinicians are knowledgeable regarding current recommendations for vitamin D supplementation in breastfeeding infants. They are also open to recommending maternal supplementation or offering parents a choice of maternal or infant vitamin supplementation.

Comparison of the effect of daily versus bolus dose maternal vitamin D3 supplementation on the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio

OBJECTIVE Supplementing lactating mothers with high doses of vitamin D3 can adequately meet vitamin D requirements of the breastfed infant. We compared the effect of bolus versus daily vitamin D3 dosing in lactating mothers on vitamin D3 catabolism. We hypothesized that catabolism of 25(OH)D3 to 24,25(OH)2D3 would be greater in the bolus than in the daily dose group. DESIGN, SETTING AND PATIENTS Randomized controlled trial (clinicaltrials.govNCT01240265) in 40 lactating women. INTERVENTIONS Subjects were randomized to receive vitamin D3 orally, either a single dose of 150,000IU or 5000IU daily for 28days. Vitamin D metabolites were measured in serum and breast milk at baseline, 1, 3, 7, 14 and 28days. MAIN OUTCOME MEASURE Temporal changes in the serum 24,25(OH)2D3/25(OH)D3 ratio. RESULTS The concentration of serum 24,25(OH)2D3 was directly related to that of 25(OH)D in both groups (r2=0.63; p<0.001). The mean (±SD) 24,25(OH)2D3/25(OH)D3 ratio remained lower at all time points than baseline values in the daily dose group (0.093±0.024, 0.084±0.025, 0.083±0.024, 0.080±0.020, 0.081±0.023, 0.083±0.018 at baseline, 1, 3, 7, 14, and 28days, respectively). In the single dose group, the increase in 24,25(OH)2D3 lagged behind that of 25(OH)D, but the 24,25(OH)2D3/25(OH)D3 values (0.098±0.032, 0.067±0.019, 0.081±0.017, 0.092±0.024, 0.103±0.020, 0.106±0.024, respectively) exceeded baseline values at 14 and 28days and were greater than the daily dose group at 14 and 28days (p=0.003). The 24,25(OH)2D3/25(OH)D3 ratio remained in the normal range with both dosing regimens. Greater breast milk vitamin D3 values in the single dose group were inversely associated with the 24,25(OH)2D3/25(OH)D3 ratio (r2=0.14, p<0.001), but not with daily dosing. CONCLUSIONS After a 14-day lag, a single high dose of vitamin D led to greater production of 24,25(OH)2D3, presumably via induction of the 24-hydroxylase enzyme (CYP24A1), relative to the 25(OH)D3 value than did daily vitamin D supplementation, and this effect persisted for at least 28days after vitamin D administration. A daily dose of vitamin D may have more lasting effectiveness in increasing 25(OH)D3 with lesser diversion of 25(OH)D3 to 24,25(OH)2D3 than does larger bolus dosing.