Analyzing Adherence to Prenatal Supplement: Does Pill Count Measure Up?
ABSTRACT Objective. To determine if adherence as measured by pill count would show a significant association with serum-based measures of adherence.
Methods. Data were obtained from a prenatal vitamin D supplementation trial where subjects were stratified by race and randomized into three dosing groups: 400 (control), 2000, or 4000 IU vitamin D3/day. One measurement of adherence was obtained via pill counts remaining compared to a novel definition for adherence using serum 25-hydroxy-vitamin D (25-OH-D) levels (absolute change in 25(OH)D over the study period and the subject's steady-state variation in their 25(OH)D levels). A multivariate logistic regression model examined whether mean percent adherence by pill count was significantly associated with the adherence measure by serum metabolite levels.
Results. Subjects' mean percentage of adherence by pill count was not a significant predictor of adherence by serum metabolite levels. This finding was robust across a series of sensitivity analyses.
Conclusions. Based on our novel definition of adherence, pill count was not a reliable predictor of adherence to protocol, and calls into question how adherence is measured in clinical research. Our findings have implications regarding the determination of efficacy of medications under study and offer an alternative approach to measuring adherence of long half-life supplements/medications.
Full-textDOI: · Available from: Thomas C Hulsey, May 27, 2015
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ABSTRACT: OBJECTIVE: To determine whether 4000 IU vitamin D(3)/day (vs. 2000 IU/day) during pregnancy is safe and improves maternal/neonatal 25(OH)D in a dose-dependent manner. STUDY DESIGN: 257 pregnant women 12-16 weeks' gestation were enrolled. Randomization to 2000- vs. 4000 IU/day followed one-month run-in at 2000 IU/day. Participants were monitored for hypercalciuria, hypercalcemia and 25(OH)D status. RESULTS: Maternal 25(OH)D (n=161) increased from 22.7(SD 9.7) at baseline to 36.2(SD 15) and 37.9(SD 13.5) in the 2000- and 4000 IU groups, respectively. While maternal 25(OH)D change from baseline did not differ between groups, 25(OH)D monthly increase differed between groups (p<0.01). No supplementation-related adverse events occurred. Mean cord blood 25(OH)D (ng/mL) was 22.1±10.3 in 2000- and 27.0±13.3 in 4000 IU group (p=0.024). After controlling for race and study site, preterm birth and labor were inversely associated with pre-delivery- and mean 25(OH)D, but not baseline 25(OH)D,. CONCLUSIONS: Maternal supplementation with 2000 and 4000 IU vitamin D/day during pregnancy improved maternal/neonatal vitamin D status. Evidence of risk reduction in infection, preterm labor and preterm birth was suggestive, requiring additional studies powered for these endpoints.American journal of obstetrics and gynecology 11/2012; 208(2). DOI:10.1016/j.ajog.2012.10.888 · 3.97 Impact Factor
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ABSTRACT: Background:Vitamin D (vD) deficiency in pregnancy is a global health problem and the amount of vD supplementation to prevent vD deficiency is controversial.Objective:Determine effectiveness and safety of prenatal 2000 IU and 4000 IU/day compared with 400 IU/day vD3 supplementation in a RCT in population where vD deficiency is endemic.Design/Methods:Arab women were randomized at 12-16 weeks of gestation to 400, 2000 and 4000 IU/day vD3 which were continued to delivery. Serum 25(OH)D concentrations were measured during pregnancy and at delivery. The primary outcome was maternal and cord blood 25(OH)D and the secondary outcomes were achievement of " sufficient" serum 25(OH)D [mteq]32 ng/ml ([mteq]80 nmol/L) at delivery.Setting:The locations were primary care and tertiary perinatal care center.Results:Of 192 enrolled, 162 (84%) continued to delivery. Mean serum 25(OH)D of 8.2 ng/ml (20.5 nmol/L) at enrollment was low. Mean serum 25(OH)D concentrations at delivery and in cord blood were significantly higher in the 2000 and 4000 IU than 400 IU/day group (p<0.001) and was highest in the 4000 IU/day group. The percent who achieved 25(OH)D >32 ng/ml and >20 ng/ml concentrations in mothers and infants was highest in 4000 IU/day group. Safety measurements were similar by group and no adverse event related to vD supplementation.Conclusions:Vitamin D supplementation of 2000 and 4000 IU/day appeared safe in pregnancy and 4000 IU/day was most effective in optimizing serum 25(OH)D concentrations in mothers and their infants. These findings could apply to other populations where vD deficiency is endemic.The Journal of Clinical Endocrinology and Metabolism 04/2013; 98(6). DOI:10.1210/jc.2013-1154 · 6.31 Impact Factor
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ABSTRACT: Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse gestational outcomes. To examine whether supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011), the International Clinical Trials Registry Platform (ICTRP) (31 October 2011), the Networked Digital Library of Theses and Dissertations (28 October 2011) and also contacted relevant organisations (8 April 2011). Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy. Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy. The search strategy identified 34 potentially eligible references. We included six trials assessing a total of 1023 women, excluded eight studies, and 10 studies are still ongoing. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation/placebo and one trial with 400 women compared the effects of vitamin D and calcium versus no supplementation.Only one trial with 400 women reported on pre-eclampsia: women who received 1200 IU vitamin D along with 375 mg of elemental calcium per day were as likely to develop pre-eclampsia as women who received no supplementation (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.33 to 1.35). Data from four trials involving 414 women consistently show that women who received vitamin D supplements had higher concentrations of vitamin D in serum at term than those women who received no intervention or a placebo; however the magnitude of the response was highly heterogenous. Data from three trials involving 463 women suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 grams than those women receiving no treatment or placebo; statistical significance was borderline (RR 0.48; 95% CI 0.23 to 1.01).In terms of other conditions, there were no significant differences in adverse side effects including nephritic syndrome (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women); stillbirths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) or neonatal deaths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) between women who received vitamin D supplements in comparison with women who received no treatment or placebo. No studies reported on preterm birth, maternal death, admission to neonatal intensive care unit/special nursery or Apgar scores. Vitamin D supplementation in a single or continued dose during pregnancy increases serum vitamin D concentrations as measured by 25-hydroxyvitamin D at term. The clinical significance of this finding and the potential use of this intervention as a part of routine antenatal care are yet to be determined as the number of high quality trials and outcomes reported is too limited to draw conclusions on its usefulness and safety. Further rigorous randomised trials are required to evaluate the role of vitamin D supplementation in pregnancy.Cochrane database of systematic reviews (Online) 01/2012; 2(2):CD008873. DOI:10.1002/14651858.CD008873.pub2 · 5.94 Impact Factor