Background The need, safety and effectiveness of vitamin D supplementation during pregnancy remain controversial. Design In this randomized controlled trial, women with a singleton pregnancy at 12–16 weeks’ gestation received 400, 2000 or 4000 IU vitamin D3/day until delivery. The primary outcome was maternal/neonatal circulating 25(OH)D at delivery, with secondary outcomes 25(OH)D ≥80 nmol/L achieved and 25(OH)D concentration required to achieve maximal 1,25(OH)2D production. Results Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D by group at delivery and 1-month before delivery were significantly different (p<0.0001), and percent who achieved sufficiency was significantly different by group, greatest in 4000 IU group (p<0.0001). The relative risk (RR) for achieving ≥80 nmol/L within one month of delivery was significantly different between 2000 vs. 400 IU (RR 1.52 [CI 1.24–1.86]); 4000 vs. 400 (RR 1.60 [CI 1.32–1.95]), but not between 4000 vs. 2000 (RR 1.06 [CI 0.93–1.19]). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)2D concentrations throughout pregnancy (p<0.0001) with maximal production of 1,25(OH)2D in all strata in the 4000 IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. Conclusions Vitamin D supplementation of 4,000 IU/day for pregnant women was safe and most effective in achieving sufficiency in all women and their neonates regardless of race while the current estimated average requirement was comparatively ineffective at achieving adequate circulating 25(OH)D, especially in African Americans.

With limited sun exposure, an intake of 400 IU/day vitamin D(3) did not sustain circulating maternal 25(OH)D levels, and thus, supplied only extremely limited amounts of vitamin D to the nursing infant via breast milk. Infant levels achieved exclusively through maternal supplementation were equivalent to levels in infants who received oral vitamin D supplementation. Thus, a maternal intake of 6400 IU/day vitamin D elevated circulating 25(OH)D in both mother and nursing infant.

OBJECTIVE: Compare effectiveness of maternal vitamin D 3 supplementation with 6400 IU per day alone to maternal and infant supplementation with 400 IU per day.METHODS: Exclusively lactating women living in Charleston, SC, or Rochester, NY, at 4 to 6 weeks postpartum were randomized to either 400, 2400, or 6400 IU vitamin D 3 /day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitamin D 3 /day; infants in 2400 and 6400 IU groups received 0 IU/day (placebo). Vitamin D deficiency was defined as 25-hydroxy-vitamin D (25(OH)D) ,50 nmol/L. 2400 IU group ended in 2009 as greater infant deficiency occurred. Maternal serum vitamin D, 25(OH)D, calcium, and phosphorus concentrations and urinary calcium/creatinine ratios were measured at baseline then monthly, and infant blood parameters were measured at baseline and months 4 and 7.RESULTS: Of the 334 mother-infant pairs in 400 IU and 6400 IU groups at enrollment, 216 (64.7%) were still breastfeeding at visit 1; 148 (44.3%) continued full breastfeeding to 4 months and 95 (28.4%) to 7 months. Vitamin D deficiency in breastfeeding infants was greatly affected by race. Compared with 400 IU vitamin D 3 per day, 6400 IU/day safely and significantly increased maternal vitamin D and 25(OH)D from baseline (P , .0001). Compared with breastfeeding infant 25(OH)D in the 400 IU group receiving supplement, infants in the 6400 IU group whose mothers only received supplement did not differ. CONCLUSIONS:Maternal vitamin D supplementation with 6400 IU/day safely supplies breast milk with adequate vitamin D to satisfy her nursing infant's requirement and offers an alternate strategy to direct infant supplementation. WHAT'S KNOWN ON THIS SUBJECT:The vitamin D concentration in breast milk of women taking 400 IU vitamin D per day is relatively low, leading to vitamin D deficiency in breastfeeding infants. As a result, the American Academy of Pediatrics recommends breastfeeding infant vitamin D supplementation within days after birth. WHAT THIS STUDY ADDS:Maternal vitamin D supplementation alone with 6400 IU/day safely supplies breast milk with adequate vitamin D to satisfy the requirement of her nursing infant and offers an alternate strategy to direct infant supplementation. Dr Hollis, as the principal investigator (PI) of the project, worked with Dr Wagner in the conception of the project, study design, implementation of the study, laboratory analyses, data analyses, and writing of the manuscript; Dr, Wagner as clinical PI of the study, worked with Drs Hollis and Howard, site PI at the University of Rochester (U of R), and all other coinvestigators in the conception of the project, study design, implementation of the study, review of clinical and laboratory data, subject safety, data analyses, and writing of the manuscript; Dr Howard as clinical site PI at the U of R worked directly with Dr Wagner; she was involved in the conception of the project, study design, implementation of the study, laboratory analyses, data analyses, and writing of the manuscript; M...

The objective was to determine the incidence of vitamin D deficiency, insufficiency, and sufficiency in African-American, Hispanic, and Caucasian pregnant women. Blood samples were taken from 154 African-American, 194 Hispanic, and 146 Caucasian women at <14 weeks of gestation; 25 hydroxyvitamin D levels (25(OH)D) levels were measured by radioimmunoassay. The mean 25(OH)D levels in African-American, Hispanic, and Caucasian pregnant women were 15.5 ± 7.2 (standard deviation), 24.1 ± 8.7, 29.0 ± 8.5 ng/mL, respectively. Ninety-seven percent of African-Americans, 81% of Hispanics, and 67% of Caucasians were deficient (25(OH)D levels <20 ng/mL or <50 nmol/L) or insufficient (25(OH)D levels ≥ 20 ng/mL or <32 ng/mL or ≥ 50 nmol/L or <80 nmol/L). Of these pregnant women, 82% had vitamin D levels <32 ng/mL (<80 ng/mL). In logistic regression models, race was the most important risk factor for vitamin D deficiency or insufficiency. African-American women and Hispanic women were more likely to have vitamin D insufficiency and deficiency than Caucasian women. Furthermore, primigravid women were more at risk for vitamin D insufficiency. This study demonstrates widespread vitamin D deficiency and insufficiency in pregnant females living at a southern latitude. African-Americans are at greatest risk.

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Objective-To assess the safety and health effects of vitamin D supplementation during pregnancy.Methods and Design-Datasets from two randomized clinical trials were first analyzed separately then combined for this analysis using a common data dictionary. In the NICHD trial, women were randomized to 400, 2000, or 4000 IU vitamin D 3 /day, stratified by race. In the Thrasher Research Fund trial, participants were randomized to 2000 or 4000 IU vitamin D 3 /day. Study drugs were from the same manufacturing lot for both trials. Identical questionnaires were given for comparable sociodemographics & clinical characteristics. Outcome measures were: (1) maternal and neonatal 25(OH)D achieved, and (2) maternal comorbidities of pregnancy (COP). SAS 9.3 was used for all analyses.Results-In the combined cohort, there were 110 controls, 201 in the 2000 IU group, and 193 in the 4000 IU group. No differences between groups in baseline 25(OH)D were found; however, delivery and cord blood values were greater in the 4000 IU group (p<0.0001), an effect that persisted even after controlling for race and study. A greater percent were vitamin D replete in the 4000 IU group (p<0.0001). There was a trend where the 4000 IU group had decreased rates of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access

Background and Objective: Intestinal permeability in preterm infants represents a critical balance between absorption of nutritional agents and protection from dangerous pathogens. This study identified the relationship between feeding type (human milk and formula) and intestinal permeability as measured by lactulose to mannitol ratio in preterm infants in the first postnatal month. Study Design: Sixty-two preterm (Յ32 weeks of gestation) infants had assessment of feeding type and evaluation with enteral lactulose and mannitol administration and urinary measurement at three time points in the first postnatal month. Results: Infants who received the majority of feeding as human milk (Ͼ75%) demonstrated significantly lower intestinal permeability when compared to infants receiving minimal or no human milk (Ͻ25% or none) at postnatal days 7, 14, and 30 (p ϭ 0.02, 0.02, and 0.047, respectively). When infants receiving any human milk were compared to infants receiving formula only, a significant difference existed at day 7 and day 14 but not for day 30 (p ϭ 0.04, 0.02, and 0.15, respectively). With evaluation over the complete study period, exclusively formulafed infants demonstrated a 2.8-fold higher composite median lactulose/mannitol ratio when compared with those who received any human milk. Infants who received Ͼ75% of enteral feeding as mother's milk demonstrated a 3.8-fold lower composite median ratio when compared to infants receiving Ͻ25% or no mother's milk. Conclusion: Preterm infant intestinal permeability was significantly decreased for those receiving human milk versus formula in a dose-related manner in the first postnatal month.

Pneumothorax is a serious complication in CF patients, occurring more commonly in older patients with more advanced lung disease. Nearly 1 in 167 patients will experience this complication each year. There is an attributable mortality to the complication and considerable morbidity, resulting in increased health-care utilization and a measurable decline in lung function.