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The patent ductus arteriosus (PDA) has long been a treatment dilemma in the field of neonatology. Standard treatment regimens have considerable side effect profiles and surgical treatment carries significant risk to the neonate. Recent studies have demonstrated that acetaminophen may be a safe and effective alternative treatment to indomethacin for PDA closure. Currently, there are very few studies that have examined safety and pharmacologic mechanisms of acetaminophen in premature infants. We conducted a …

Pregnancy represents a dynamic period with physical and physiological changes in both the mother and her developing fetus. The dramatic 2–3 fold increase in the active hormone 1,25(OH)2D concentrations during the early weeks of pregnancy despite minimal increased calcium demands during that time of gestation and which are sustained throughout pregnancy in both the mother and fetus suggests an immunomodulatory role in preventing fetal rejection by the mother. While there have been numerous observational studies that support the premise of vitamin D's role in maintaining maternal and fetal well-being, until recently, there have been few randomized clinical trials with vitamin D supplementation. One has to exhibit caution, however, even with RCTs, whose results can be problematic when analyzed on an intent-to-treat basis and when there is high non-adherence to protocol (as if often the case), thereby diluting the potential good or harm of a given treatment at higher doses. As such, a biomarker of a drug or in this case “vitamin” or pre-prohormone is better served. For these reasons, the effect of vitamin D therapies using the biomarker circulating 25(OH)D is a far better indicator of true “effect.” When pregnancy outcomes are analyzed using the biomarker 25(OH)D instead of treatment dose, there are notable differences in maternal and fetal outcomes across diverse racial/ethnic groups, with improved health in those women who attain a circulating 25(OH)D concentration of at least 100 nmol·L−1 (40 ng·mL−1). Because an important issue is the timing or initiation of vitamin D treatment/supplementation, and given the potential effect of vitamin D on placental gene expression and its effects on inflammation within the placenta, it appears crucial to start vitamin D treatment before placentation (and trophoblast invasion); however, this question remains unanswered. Additional work is needed to decipher the vitamin D requirements of pregnant women and the optimal timing of supplementation, taking into account a variety of lifestyles, body types, baseline vitamin D status, and maternal and fetal vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genotypes. Determining the role of vitamin D in nonclassical, immune pathways continues to be a challenge that once answered will substantiate recommendations and public health policies. Larger amounts of vitamin D are needed during pregnancy than are currently recommended assert two experts. In a review article, Bruce Hollis and Carol Wagner from the Medical University of South Carolina in Charleston, USA, argue that current guidelines regarding vitamin D levels during pregnancy fail to take into account the latest research showing that vitamin D supplementation can help protect both the mother from pregnancy-related complications and the developing fetus from autoimmune disorders. The authors describe how, apart from its usual function as a calcium-regulating factor, vitamin D during pregnancy primarily helps maintain a proper immune balance. They argue that a lack of vitamin D during pregnancy or the early months of infancy may be responsible for certain diseases in later life, including asthma and multiple sclerosis.

OBJECTIVE: To identify the vitamin D status to optimize calcium and bone health in preterm infants. STUDY DESIGN: Very low birth weight infants had measurement of 25-hydroxyvitamin D status and markers of calcium and bone health from birth to term age. Piecewise linear regression modeling was performed to identify a 25-hydroxyvitamin D threshold associated with stable parathyroid hormone concentration and bone mineralization. RESULTS: In a cohort of 89 infants at term age, femur BMC and density increased linearly with 25-hydroxyvitamin D status until reaching a threshold of 48 ng/mL and 46 ng/mL, respectively. Parathyroid hormone status decreased as vitamin D status increased until reaching a plateau at 25-hydroxyvitamin D of 42 ng/mL. CONCLUSION: Preterm infant vitamin D status was significantly associated with PTH status and femur mineralization with suggestion that achieving a specific 25-hydroxyvitamin concentration is associated with optimal calcium homeostasis and femur bone mineralization.

Background Three previous reviews on the association of vitamin D insufficiency in pregnancy with preterm birth (PTB) and stillbirth were limited in scope and deemed inconclusive. With important new evidence accumulating, there is the need to update the previous estimates and assess evidence on other clinically important outcomes such as spontaneous abortion and Apgar score. We conducted a systematic review and meta-analysis to evaluate the quality and strength of the available evidence on the relations between vitamin D nutritional status, and pregnancy and birth outcomes. Methods PubMed and Scopus databases were searched from their inception to June, 2015 with no language restrictions imposed. Eighteen longitudinal studies satisfied the inclusion criteria. Random effects model was applied in computing the summary effect estimates and their corresponding 95% confidence intervals. Results Serum 25(OH)D levels

The evolutionary patterns of human migration and historical pre/post-industrial revolution have changed the face of bone metabolic disease through past centuries. Cultural, religious, and lifestyle practices continue to alter nutritional recommendations for this expanding diagnosis. Likewise, modern advancements in the field of neonatology and, more specifically, aggressive nutritional management of premature infants have shaped the epidemiology of neonatal bone metabolism over the past two decades. Decreased use of long-term parenteral nutrition, early fortification of enteral nutrition, and stringent American Academy of Pediatrics (AAP) practice guidelines instituting early supplementation of vitamin D have attributed to improved bone mineralization outcomes in both term and preterm infants. Nevertheless, neonatal bone mineral metabolic disorders remain prevalent. In this review, we provide an in-depth look at the diagnoses, therapeutics, and subset populations-both genetic and non-genetic-affected by neonatal bone mineral metabolic disorders.

OBJECTIVES: We have previously found that vitamin D supplementation may slow down epigenetic aging in young adults. Recently, new epigenetic clocks have been developed to estimate gestational age in newborn babies. We tested the hypothesis that vitamin D supplementation would slow down the epigenetic gestational aging. METHODS: A total of 92 participants (51% whites, 21% blacks, 28% Hispanics) were randomly selected from 450 pregnant women who were enrolled in a randomized controlled trial. Each mother was randomized to receive either 4000 IU/day vitamin D(3) or placebo plus the standard prenatal vitamins containing 400 IU vitamin D(3). Cord blood genome-wide methylation analyses were performed on the Illumina Infinium MethylationEPIC Beadchip. DNA methylation gestational age (DNAmGA) was calculated based on two methods developed by Knight and Bohlin. The effects of vitamin D(3) supplementation on DNA methylation-based gestational age acceleration (∆DNAmGA) were estimated in linear regressions adjusted for maternal age, race, smoking status and sex of the babies. RESULTS: Gestational age was highly correlated with DNAmGA(Knight) and DNAmGA(Bohlin) having the same correlation coefficients of 0.88 (ps

The objective of this investigation was to compare bioavailability between single oral dose Vitamin D3 (vitD3) gummies vs. tablets in healthy adults. An initial crossover, randomized clinical trial involving healthy adults (n = 9) was conducted followed by a larger, confirmatory study (n = 31). Healthy participants aged 18&ndash, 45 years with body mass index (BMI) 18&ndash, 30 without anemia or vitD deficiency were randomized to receive 20,000 international units (IU) vitD3 as single dose gummies or tablets with serial samples obtained to measure plasma vitD3 at baseline, 3, 6, 10, 24, and 48 h followed by a 2-week washout period. The same participants then crossed over to receive 20,000 IU vitD3 in the form not previously given, with sampling at the same time points. Deidentified blood samples were analyzed for vitD3 concentration by liquid chromatography (LC)-mass spectroscopy. In Study 1, results suggested bioavailability was greater with gummies compared with tablets, (effect size 1.08 at 24 h). In Study 2, the area under the concentration curve (AUC) was higher with gummies than tablets (gummy mean (95% CI): 1474 ng&middot, /mL (1393&ndash, 1555), tablet mean (95% CI): 774 ng&middot, h/mL (693&ndash, 855), p &lt, 0.0001). Average peak blood concentration (Cmax) values were significantly higher with gummies (gummy: 47.3 ng/mL, tablet: 23.4 ng/mL, p &lt, 0.0001). VitD3 gummies had greater bioavailability than tablets with higher vitD concentrations over time, which may have implications for achieving vitD sufficiency.

Objective: Sex is an important determinant of neonatal outcomes and may have a significant role in the physiologic response to maternal chorioamnionitis. Our goal was to determine cerebral blood flow (CBF) parameters by sex and subsequent neurodevelopment in healthy term infants exposed to chorioamnionitis. Study Design: CBF by Doppler ultrasound in anterior and middle cerebral (ACA, MCA) and basilar arteries were analyzed for time-averaged maximum velocity (TAMX) and corrected resistive index in 52 term control and chorioamnionitis-exposed infants between 24 and 72 h after birth. Placental pathology confirmed histologic evidence of chorioamnionitis (HC). Bayley Scales of Infant Development-III were administered at 12 months. Result: HC male infants had significantly greater TAMX in the MCA and lower mean MCA and ACA resistance than HC females. Abnormal CBF correlated negatively with neurodevelopmental outcome. Conclusion: CBF is altered in term infants with histologically confirmed chorioamnionitis compared with control infants with sex-specific differences.

Context: There is no doubt that vitamin D must be activated to the hormonal form 1,25-dihydroxyvitamin D to achieve full biological activity or that many tissues participate in this activation process—be it endocrine or autocrine. We believe that not only is 25-hydroxyvitamin D important to tissue delivery for this activation process, but also that intact vitamin D has a pivotal role in this process. Objective: In this review, evidence on the vitamin D endocrine/autocrine system is presented and discussed in relation to vitamin D-binding protein affinity, circulating half-lives, and enzymatic transformations of vitamin D metabolites, and how these affect biological action in any given tissue. Conclusions: Circulating vitamin D, the parent compound, likely plays an important physiological role with respect to the vitamin D endocrine/autocrine system, as a substrate in many tissues, not originally thought to be important. Based on emerging data from the laboratory, clinical trials, and data on circulating 25-hydroxyvitamin D amassed during many decades, it is likely that for the optimal functioning of these systems, significant vitamin D should be available on a daily basis to ensure stable circulating concentrations, implying that variation in vitamin D dosing schedules could have profound effects on the outcomes of clinical trials because of the short circulating half-life of intact vitamin D.

Objectives:To determine systemic hypothermia’s effect on circulating immune cells and their corresponding chemokines after hypoxic ischemic encephalopathy in neonates.Design:In our randomized, controlled, multicenter trial of systemic hypothermia in neonatal hypoxic ischemic encephalopathy, we measu

In recent years, vitamin D has been received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries and the identification of extraskeletal effects of vitamin D, suggesting unexpected benefits of vitamin D in health and disease, beyond bone health. The possibility of extraskeletal effects of vitamin D was first noted with the discovery of the vitamin D receptor (VDR) in tissues and cells that are not involved in maintaining mineral homeostasis and bone health, including skin, placenta, pancreas, breast, prostate and colon cancer cells, and activated T cells. However, the biological significance of the expression of the VDR in different tissues is not fully understood, and the role of vitamin D in extraskeletal health has been a matter of debate. This report summarizes recent research on the roles for vitamin D in cancer, immunity and autoimmune diseases, cardiovascular and respiratory health, pregnancy, obesity, erythropoiesis, diabetes, muscle function, and aging.

Milk is successfully produced by mothers regardless of their nutritional status. Nevertheless, the concentrations of some nutrients, specifically vitamins A, D, B1, B2, B3, B6, and B12, fatty acids, and iodine, in human milk depend on or are influenced by maternal diet. A healthy and varied diet during lactation ensures adequate maternal nutrition and optimal concentration of some nutrients in human milk. Exclusive breastfeeding meets the nutritional needs of infants for 6 months of life with the exception of vitamins D and K, which should be given to breastfed infants as supplements.

Background: The effect of latitude on maternal and infant vitamin D status during lactation is presumed to be strongly associated with higher rates of deficiency in those living at higher latitudes, yet with lifestyle changes, this conclusion may no longer be correct. Objective: To ascertain if higher latitude adversely affects the vitamin D status of lactating women and their fully breastfeeding infants. Study Design/Methods: Fully breastfeeding women and their infants were eligible for participation in this study as part of a larger prospective vitamin D supplementation trial. Women were recruited from two sites of differing latitude: Charleston, SC at 32˚N and Rochester, NY at latitude 43˚N. Maternal and infant baseline vitamin D status, intact parathyroid hormone (IPTH), serum calcium and phosphorus as a function of site/latitude were measured. The primary outcome was maternal and infant total circulating 25(OH)D at baseline by center/latitude, and the secondary outcome was the percent of women and infants who had achieved a baseline concentration of at least 20 ng/mL, meeting the Institute of Medicine’s definition of sufficiency at 4 to 6 weeks postpartum. Statistical analysis was performed using SAS version 9.3. Results: Higher latitude adversely affected vitamin D status only in lactating Caucasian women. African American and Hispanic women and infants living in Rochester compared to Charleston had improved vitamin D status, an effect that was no longer significant when controlling for socioeconomic factors and season. Overall, there was a significant vitamin D deficiency at baseline in lactating mothers, and a far greater deficiency in their infants. Maternal baseline 25(OH)D concentration remained positively associated with being Caucasian, BMI and summer months. Breastfeeding infant vitamin D status mirrored maternal status and remained positively associated with being Caucasian and summer months. Those infants who had been on a vitamin D supplement at the time of enrollment in the study had markedly improved vitamin D status compared to those infants not on supplement, but represented a significant minority of the cohort. Conclusions: There was a significant vitamin D deficiency among a cohort of women and their infants living at two diverse latitudes—Charleston, SC and Rochester, NY. Given the higher rate of vitamin D deficiency among African American and Hispanic women and their infants living at a lower latitude, conclusions about vitamin D status based on latitude alone may be faulty.

Pregnancy represents a time of rapid change, including dramatic shifts in vitamin D metabolism. Circulating concentrations of the active form of vitamin D-1,25(OH)2D skyrocket early in pregnancy to levels that would be toxic to a nonpregnant adult, signaling a decoupling of vitamin D from the classic endocrine calcium metabolic pathway, likely serving an immunomodulatory function in the mother and her developing fetus. In this review, we summarize the unique aspects of vitamin D metabolism and the data surrounding vitamin D requirements during this important period. Both observational and clinical trials are reviewed in the context of vitamin D's health effects during pregnancy that include preeclampsia, preterm birth, and later disease states such as asthma and multiple sclerosis. With enhanced knowledge about vitamin D's role as a preprohormone, it is clear that recommendations about supplementation must mirror what is clinically relevant and evidence-based. Future research that focuses on the critical period(s) leading up to conception and during pregnancy to correct deficiency or maintain optimal vitamin D status remains to be studied. In addition, what effects vitamin D has on genetic signatures that minimize the risk to the mother and her developing fetus have not been elucidated. Clearly, while there is much more research that needs to be performed, our understanding of vitamin D requirements during pregnancy has advanced significantly during the last few decades.

BACKGROUND Body composition is a key metric for assessing nutrition in preterm infants. In many neonatal intensive care units body composition is estimated using anthropometric indices which mathematically combine body weight and length. However, the accuracy of these indices is unknown in preterm infants. In contrast, air-displacement plethysmography (ADP) has been shown to accurately measure neonatal fat mass, but it is not widely available. OBJECTIVE The aim was to determine which anthropometric index is most correlated to infant fat mass, as determined by ADP. DESIGN We performed a retrospective observational study, comparing ADP-determined percent body fat at 366 time points for 239 preterm infants (born

Introduction Maternal circulating 25-hydroxyvitamin D [25(OH)D] has been shown to optimize production of 1,25-dihydroxyvitamin D [1,25(OH)2D] during pregnancy at approximately 100 nmoles/L, which has pronounced effects on fetal health outcomes. Additionally, associations are noted between low maternal 25(OH)D concentrations and vascular pregnancy complications, such as preeclampsia. To further elucidate the effects of vitamin D activity in pregnancy, we investigated the role of maternal 25(OH)D, the nutritional indicator of vitamin D status, in relation to placental maintenance and, specifically, expression of placental gene targets related to angiogenesis and vitamin D metabolism. Methods A focused analysis of placental mRNA expression related to angiogenesis, pregnancy maintenance, and vitamin D metabolism was conducted in placentas from 43 subjects enrolled in a randomized controlled trial supplementing 400 IU or 4400 IU of vitamin D3 per day during pregnancy. Placental mRNA was isolated from biopsies within one hour of delivery, followed by quantitative PCR. We classified pregnant women with circulating concentrations of Results Soluble FMS-like tyrosine kinase 1 (sFlt-1) and vascular endothelial growth factor (VEGF) gene expression was significantly downregulated in the maternal subgroup with circulating 25(OH)D ≥100 ng/mL compared to the subgroup Discussion Here, we report a significant association between maternal vitamin D status and the expression of sFlt-1 and VEGF at the mRNA level. Achieving maternal circulating 25(OH)D ≥100 nmoles/L suggests the impact of maternal vitamin D3 supplementation on gene transcription in the placenta, thereby potentially decreasing antiangiogenic factors that may contribute to vascular pregnancy complications.

Objective Decreased maternal 25-hydroxyvitamin D (25-OH-D) and placenta growth factor (PlGF) have both been associated with the diagnosis of early onset severe preeclampsia (EOSPE). This investigation aimed to define the association of these biomarkers with EOSPE. Study Design Patients with EOSPE (n = 40) and healthy controls (n = 40) were recruited and information on demographics, outcomes, and plasma was collected at diagnosis of EOSPE or gestational age-matched controls. 25-OH-D was assessed by radioimmunoassay and reported in nanogram per milliliter. PlGF was assessed by enzyme-linked immunosorbent assay and reported in picogram per milliliter. Kruskal-Wallis test was used to compare biomarkers between groups. Multivariable logistic regression was used to determine associations between 25-OH-D or PlGF and the diagnosis of EOSPE. Results In EOSPE, both 25-OH-D and PlGF were decreased significantly compared with controls. After controlling for age, race, body mass index, and gestational age at sample collection, both 25-OH-D (adjusted odds ratio 0.14 [0.05, 0.36]) and PlGF (adjusted odds ratio 0.03 [0.01, 0.24] were significantly associated with diagnosis of ESOPE (p Conclusion PlGF and 25-OH-D are both associated with the diagnosis of EOSPE. These biomarkers may be helpful in development of novel rapid diagnostic tests for preeclampsia.

Background: African Americans suffer disproportionately from diabetes and cardiovascular disease and are significantly more likely to have suboptimal concentrations of circulating 25-hydroxyvitamin D [25(OH)D]. The results of epidemiologic and observational studies suggest that there is a link between vitamin D deficiency and the risk of cardiometabolic disorders, which underscores the importance of maintaining healthy concentrations of 25(OH)D. Objective: The objective was to investigate whether daily supplementation with 4000 IU vitamin D(3) for 1 y would eliminate any disparities in circulating concentrations of 25(OH)D between African American and white men. Design: Serum concentrations of 25(OH)D were measured every 2 mo in 47 subjects who received a daily oral dose of 4000 IU vitamin D(3) for 1 y. Results: More than 90% of African Americans had serum concentrations of 25(OH)D

The function and requirement of vitamin D during pregnancy for both mother and fetus have remained a mystery. This fact was highlighted by The Cochrane Review in 2000, which reported a lack of randomized controlled trials (RCTs) with respect to vitamin D requirements during pregnancy. Unfortunately, during the past decade only a single RCT has been performed with respect to vitamin D requirements during pregnancy. In this review we will discuss vitamin D metabolism during pregnancy as well as the consequences of vitamin D deficiency on skeletal, nonskeletal, and birth outcomes using birth observational data and data from our recent RCT. New RCT data strongly support previous observational studies in that improving nutritional vitamin D status will improve birth outcomes. The new RCT data indicate that 4,000 IU/day vitamin D(3) during pregnancy will "normalize" vitamin D metabolism and improve birth outcomes including primary cesarean section and comorbidities of pregnancy with no risk of side effects.

Pregnancy is a critical time in the lifecycle of a woman where she is responsible not only for her own well-being, but also that of her developing fetus, a process that continues during lactation. Until recently, the impact of vitamin D status during this period had not been fully appreciated. Data regarding the importance of vitamin D in health have emerged to challenge traditional dogma, anD'suggest that vitamin D – through its effect on immune function anD'surveillance – plays a role beyond calcium and bone metabolism on the health status of both the mother and her fetus. Following birth, this process persists; the lactating mother continues to be the main source of vitamin D for her infant. Thus, during both pregnancy and lactation, maternal deficiency predicts fetal and infant deficiency; the significance of this is just beginning to be understood and will be highlighted in this review.

Compare customized versus population-based growth curves for identification of small-for-gestational-age (SGA) and body fat percent (BF%) among preterm infants.Prospective cohort study of 204 preterm infants classified as SGA or appropriate-for-gestational-age (AGA) by population-based and customized growth curves. BF% was determined by air-displacement plethysmography. Differences between groups were compared using bivariable and multivariable linear and logistic regression analyses.Customized curves reclassified 30% of the preterm infants as SGA. SGA infants identified by customized method only had significantly lower BF% (13.8 ± 6.0) than the AGA (16.2 ± 6.3, p = 0.02) infants and similar to the SGA infants classified by both methods (14.6 ± 6.7, p = 0.51). Customized growth curves were a significant predictor of BF% (p = 0.02), whereas population-based growth curves were not a significant independent predictor of BF% (p = 0.50) at term corrected gestational age.Customized growth potential improves the differentiation of SGA infants and low BF% compared with a standard population-based growth curve among a cohort of preterm infants.

Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D’s indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered.

PURPOSE OF REVIEW: The topic of vitamin D supplementation during pregnancy is very controversial. This review attempts to provide balanced knowledge with respect to this topic gained in the past 18 months. RECENT FINDINGS: Two recent reports, one by the Institute of Medicine, and one by The Endocrine Society are greatly divergent with respect to the nutritional requirement for vitamin D, as well as, the level of circulating 25-hydroxyvitamin D that is desirable. These recommendations will be discussed along with recent observational data and a recently completed randomized controlled trial dealing with vitamin D requirements during pregnancy. SUMMARY: Current evidence supports the concept that circulating 25-hydroxyvitamin D should be 40–60 ng/ml (100–150 nmol) during pregnancy and a daily intake of 4000 IU vitamin D(3) is required to attain that circulating level.

Vitamin D recommendations are shifting. The Institute of Medicine recently revised the Estimated Average Requirement (EAR) from 200 to 400 international units (IU), the Recommended Dietary Allowance (RDA) from 400 to 600 international units (IU), and increased the Tolerable Upper Intake Level (UL) from 2,000 to 4,000 IU per day. What does this mean for the pregnant and lactating woman? To answer this question, current guidelines are described and adapted excerpts from a recent book on the subject are provided.

Importance Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. Objective To assess the effectiveness of 2 vitamin D dosing strategies in preventing recurrent wheezing. Design, Setting, and Participants A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks’ gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. Interventions Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. Main Outcomes and Measures Recurrent wheezing by 12 months’ adjusted age was the primary outcome. Results Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, −10.7% [95% CI, −27.4% to −2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, −1.6% [95% CI, −17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, −3.6% [95% CI, −16.4% to 4.4%]). Conclusions and Relevance Among black infants born preterm, sustained supplementation with vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months’ adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of vitamin D supplementation on wheezing in children born preterm. Trial Registration ClinicalTrials.gov Identifier:NCT01601847

Objectives To assess the validity of body mass index (BMI) and age- and sex-standardized BMI z-score (BMIZ) as surrogates for adiposity (body fat percentage [BF%], fat mass, and fat mass index [kg/m2]) at 3 time points in infancy (1, 4, and 7 months) and to assess the extent to which the change in BMIZ represents change in adiposity. Study design We performed a secondary analysis of 447 full-term infants in a previous trial of maternal vitamin D supplementation during lactation. Study staff measured infant anthropometrics and assessed body composition with dual-energy x-ray absorptiometry at 1, 4, and 7 months of age. We calculated Spearman correlations (rs) among BMI, BMIZ, and adiposity at each time point, and between change in BMIZ and change in adiposity between time points. Results Infants (N = 447) were 52% male, 38% white, 31% black, and 29% Hispanic. The BMIZ was moderately correlated with BF% (rs = 0.43, 0.55, 0.48 at 1, 4, and 7 months of age, respectively). BMIZ correlated more strongly with fat mass and fat mass index, particularly at 4 and 7 months of age (fat mass rs = 0.72-0.76; fat mass index rs = 0.75-0.79). Changes in BMIZ were moderately correlated with adiposity changes from 1 to 4 months of age (rs = 0.44 with BF% change; rs = 0.53 with fat mass change), but only weakly correlated from 4 to 7 months of age (rs = 0.21 with BF% change; rs = 0.27 with fat mass change). Conclusions BMIZ is moderately correlated with adiposity in infancy. Changes in BMIZ are a poor indicator of adiposity changes in later infancy. BMI and BMIZ are limited as surrogates for adiposity and especially adiposity changes in infancy. Trial Registration ClinicalTrials.gov : NCT00412074 .

The 2008 revised American Academy of Pediatrics (AAP) recommendation for 400 IU/day vitamin D intake makes progress toward achieving infant vitamin D sufficiency in the United States. Further study, however, is needed both to define vitamin D sufficiency for preterm infants based on markers of vitamin D biologic function and to develop supplementation strategies to ensure adequate vitamin D intake and, thus, vitamin D sufficiency in this at-risk population. In this review, we highlight some of the issues surrounding vitamin D status of the neonate and the particular risks for the preterm infant. We review the evidence regarding the impact of vitamin D deficiency in this population and the safety and efficacy of vitamin D supplementation. Based on previous study in preterm infants, the current AAP guidelines to achieve serum 25-hydroxyvitamin D [25(OH)D] status of at least 50 nmol/L and to receive at least 400 IU/day are safe and possibly adequate. Because of the nutritional difficulties in achieving consistent delivery of 400 IU/day of vitamin D in the preterm infant, it is imperative to devise strategies for close monitoring of each preterm infant's vitamin D status and consider oral vitamin D supplementation as an important adjunct to dietary sources and multivitamin preparations.

How human milk as the ideal infant nutrition lacks vitamin D activity leading to the severe bony deformities and muscle weakness of rickets has stymied scientists and clinicians for centuries. Recent understanding of human vitamin D requirements based on functional indicators of vitamin D activity demonstrate that the majority of humans, including lactating mothers, subsist in a vitamin D insufficient state. In this state, human milk provides inadequate vitamin D supply to the nursing infant. In contrast, with achieving maternal vitamin D sufficiency, human milk attains vitamin D activity equivalent to present infant oral supplementation. Current investigation of the role of vitamin D in diseases beyond bone health is revealing the significance of early life vitamin D sufficiency in establishing lifelong health.

The gut represents a complex organ system with regional differences, which reflect selective digestive and absorptive functions that change constantly in response to bodily requirements and the outside milieu. As a barrier to the external environment, gut epithelium must be renewed rapidly and repeatedly. Growth and renewal of gut epithelial cells is dependent on controlled cell stimulation and proliferation by a number of signaling processes and agents, including gut peptides-both endogenous and exogenous sources. This cascade of events begins during fetal development; with the ingestion of amniotic fluid, this process is enhanced and continued during infancy and early childhood through the ingestion of human milk. Events influenced by amniotic fluid during fetal development and those influenced by human milk that unfold after birth and early childhood to render the gut mature are presented.

Mothers of hospitalized premature infants who choose to provide breast milk are at increased risk of an inadequate breast milk supply. When nonpharmacologic interventions to increase milk supply fail, clinicians are faced with limited options. There is no current evidence to support the use of herbal galactogogues in this population and a black box warning for metoclopramide for potential serious side effects. Thus, domperidone was the only known, effective option for treatment of low milk supply in this population. With a thorough review of the literature on domperidone and coordination with the obstetrical, neonatal, lactation, and pharmacology teams, a domperidone treatment protocol for mothers of hospitalized premature infants with insufficient milk supply was developed at our institution and is presented in this article. A comprehensive understanding of domperidone for use as a galactogogue with a standard treatment protocol will facilitate safer prescribing practices and minimize potential adverse reactions in mothers and their hospitalized premature infants.

Cathelicidin is an antimicrobial peptide whose circulating levels are related to vitamin D status in adults. This study sought to determine if circulating cathelicidin concentrations in healthy children are related to the age of the child, body composition and vitamin D status at birth and at the time of the study visit. Blood samples were obtained during yearly visits from 133 children, ages 2-7, whose mothers had participated in a pregnancy vitamin D supplementation RCT. Radioimmunoassay and ELISA were performed to analyze 25(OH)D and cathelicidin, respectively. Statistical analyses compared cathelicidin concentrations with concentrations of 25(OH)D at various time points (maternal levels throughout pregnancy, at birth, and child's current level); and with race/ethnicity, age, gender, BMI, percent fat, and frequency of infections using Student's t-test, χ2, Wilcoxon ranked-sum analysis, and multivariate regression. The cohort's median cathelicidin concentration was 28.1 ng/mL (range: 5.6-3368.6) and did not correlate with 25(OH)D, but was positively correlated with advancing age (ρ = 0.236 & p = 0.005, respectively). Forty patients evaluated at two visits showed an increase of 24.0 ng/mL in cathelicidin from the first visit to the next (p

The purpose of this feasibility study was to investigate the correlation of a salivary occult blood test (SOBT) with traditional periodontal measures to assess the feasibility of the SOBT as a measure of periodontal inflammation in a population of women during pregnancy. Considering the limitations of the previous SOBT studies, this study evaluated correlation of the Perioscreen Sunstar SOBT with traditional measures from a full mouth periodontal examination. Data were collected 3 times during pregnancy (12-14, 24-28, and 36 weeks) from women participating in an ongoing study of pregnancy and inflammation. Descriptive statistics and correlations were generated for SOBT scores with periodontal measures. Preliminary data were analyzed from 7 women with 3 visits, 7 with 2, and 9 with 1 visit. For these 44 visits' data, the mean percent of sites with bleeding on probing (BOP) for SOBT scores = 0, 2, and 5 was 58% ± 18%, 68% ± 14%, and 72% ± 19%, respectively. Correlations for percent of sites with BOP and continuous SOBT score was 0.301, P-value = 0.0469 and dichotomous SOBT was 0.32, P-value = 0.0339. Results for feasibility, measured as recruitment of participants, acceptance of protocols, distribution of periodontal inflammation and preliminary correlations, support SOBT as a correlated marker of periodontal inflammation in this population of pregnant women.

Despite the higher prevalence of vitamin D deficiency in blacks, the vitamin D status of black preterm infants remains unknown. In addition, with the combination of parenteral and enteral nutritional support that preterm infants receive, the effect of vitamin D-deficient breast milk on vitamin D status is unknown.To evaluate vitamin D status of preterm infants through the first month after delivery and compare status by race and feeding type.Thirty-six (36) preterm (or =32 weeks gestation) infants (19 black, 17 white) had assessment of feeding type, vitamin D intake, and serum 25-hydroxyvitamin D [25(OH)D] as a marker of vitamin D status at three time points in the first month after delivery.Black infants had a significantly lower mean 25(OH)D level on day 7-8 and day 14-15 evaluations than white infants [14.9 +/- 6.6 versus 23.3 +/- 9.3 ng/mL (p = 0.021) and 18.3 +/- 7.3 versus 25.6 +/- 10.3 ng/mL (p = 0.048), respectively], but the difference was no longer significant by day 28-30 evaluation [19.6 +/- 7.7 versus 26.2 +/- 11.6 ng/mL (p = 0.26)]. Vitamin D status was not significantly lower in infants receiving predominantly breast milk (p = 0.6). Vitamin D intake rose through the month as the amount and caloric density of enteral nutrition increased. Six infants had significant decrease in serum 25(OH)D values from day 14-15 to day 28-30 evaluation despite receiving400 IU/day vitamin D.Differences in vitamin D status occurred between black and white infants and were significant through the first 2 weeks after delivery. Infants receiving predominantly breast milk did not have significantly worse vitamin D status than those receiving formula. The significant decline in serum 25(OH)D status observed in 28% of the infants was not related to breast milk intake.

Improve vitamin D status in lactating women and their recipient infants, and measure breast milk calcium concentration [Ca] as a function of vitamin D regimen.Fully breastfeeding mothers were randomized at 1 month postpartum to 2000 (n = 12) or 4000 (n = 13) IU/day vitamin D for 3 months to achieve optimal vitamin D status [serum 25(OH)Dor =32 ng/mL (80 nmol/L)]. Breast milk [Ca], maternal and infant serum 25(OH)D and serum Ca, and maternal urinary Ca/Cr ratio were measured monthly.Mothers were similar between groups for age, race, gestation, and birth weight. 25(OH)D increased from 1 to 4 months in both groups (mean +/- SD): +11.5 +/- 2.3 ng/mL for group 2000 (p = 0.002) and +14.4 +/- 3.0 ng/mL for group 4000 (p = 0.0008). The 4000 IU/day regimen was more effective in raising both maternal and infant serum levels and breast milk antirachitic activity than the 2000 IU/day regimen. Breast milk [Ca] fell with continued lactation through 4 months in the 2000 and 4000 IU groups. Decline in breast milk [Ca] was not associated with vitamin D dose (p = 0.73) or maternal 25(OH)D (p = 0.94). No mother or infant experienced vitamin D-related adverse events, and all laboratory parameters remained in the normal range.High-dose vitamin D was effective in increasing 25(OH)D levels in fully breastfeeding mothers to optimal levels without evidence of toxicity. Breast milk [Ca] and its decline in both groups during 1 to 4 months were independent of maternal vitamin D status and regimen. Both the mother and her infant attained improved vitamin D status and maintained normal [Ca].

The objective of the study was to measure the impact of personality and other factors on the decision to initiate breastfeeding. Mothers were enrolled (24-96 hours postpartum) and were classified as fully breastfeeding, formula-feeding, or combination-feeding. A semi-structured interview about maternal sociodemographics and attitudes and a standardized personality inventory (NEO-PI-R) were conducted. Eighty-seven mothers completed the study: 50 breastfeeders, 6 combination feeders, and 31 formula feeders. Because of small numbers, combination-feeder mothers (n = 6) were excluded from analyses. Maternal age, marriage, ethnicity, and socioeconomic status were significantly associated with breastfeeding. Breastfeeding and formula-feeding groups differed on 3 personality domains: extraversion (53.3 breastfeeding vs 46.9 formula-feeding, P = .002), openness (51.6 vs 46.2, P = .008), and agreeableness (48.5 vs 41.5, P = .01). In a multiple variable logistic regression model, extraversion ( P = .03) and openness ( P = .003) remained significant. Sociodemographics, experiential factors, and specific personality characteristics of mother were independently associated with maternal feeding decision.

Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury, but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth. This study reports a multicenter, randomized, controlled, pilot trial of moderate systemic hypothermia (33 degrees C) vs normothermia (37 degrees C) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event. The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers, and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vineland tests between normothermic and hypothermic groups. Thirty-two hypothermic and 33 normothermic neonates were enrolled. The entry criteria selected a severely affected group of neonates, with 77% Sarnat stage III. Ten hypothermia (10/32, 31%) and 14 normothermia (14/33, 42%) patients expired. Controlling for treatment group, outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers (odds ratio 10.7, 95% confidence interval 1.3-90). Severely abnormal motor scores (Psychomotor Development Index70) were recorded in 64% of normothermia patients and in 24% of hypothermia patients. The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group (52%) than the normothermia group (84%) (P = 0.019). Although these results need to be validated in a large clinical trial, this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury.

During pregnancy, immune activity is tightly regulated so that antimicrobial protection of the mother and fetus is balanced with the need for immune tolerance to prevent fetal rejection. In this setting, the maternal–fetal interface, in the form of the uterine decidua, provides a heterogeneous immune cell population with the potential to mediate diverse activities throughout pregnancy. Recent studies have suggested that vitamin D may be a key regulator of immune function during pregnancy, with the fetal–maternal interface representing a prominent target. Among its non-classical actions are potent immunomodulatory effects, including induction of antibacterial responses and modulation of T-lymphocytes to suppress inflammation and promote tolerogenesis. Thus, vitamin D may play a pivotal role in normal decidual immune function by promoting innate responses to infection, while simultaneously preventing an over-elaboration of inflammatory adaptive immunity. Research to date has focused upon the potential role of vitamin D in preventing infectious diseases such as tuberculosis, as well as possibly suppressing of autoimmune disease. Nevertheless, vitamin D may also influence facets of immune function not immediately associated with primary innate responses. This review summarises our current understanding of decidual immune function with respect to the vitamin D metabolism and signalling, and as to how this may be affected by variations in maternal vitamin D status. There has recently been much interest in vitamin D supplementation of pregnant women, but our knowledge of how this may influence the function of decidua remains limited. Further insight into the immunomodulatory actions of vitamin D during pregnancy will help shed light upon this.