Carol L Wagner

Medical University of South Carolina | MUSC · Department of Pediatrics

Unlabelled: The American Academy of Pediatrics recommends premedication for all nonemergent neonatal intubations, yet there remains significant variation in this practice nationally. We aimed to standardize our unit's premedication practices for improved intubation success and reduced adverse events. Methods: The study workgroup developed educat...

Body composition analysis to distinguish between fat mass and fat-free mass is an established research approach to assess nutritional status. Within neonatal medicine, preterm infant body composition is linked with later health outcomes including neurodevelopment and cardiometabolic health. Mounting evidence establishing fat-free mass as an indicat...

Objective Compare costs of hospitalization between critically-ill neonates with patent ductus arteriosus (PDA) who did and did not develop acute kidney injury (AKI). Study design Using the Children’s Hospital Association’s Pediatric Health Information System (PHIS) database, we ascertained the marginal estimated total cost of hospitalization betwe...

Human milk, the best enteral selection for a preterm infant, becomes altered during freezing and soluble free fatty acid is generated over time. Free fatty acids may form complexes, such as the oleic acid-bound protein called HAMLET (human α-lactalbumin made lethal to tumor cells). We determined the in vitro biological activity of preterm human mil...

Purpose Ethanolamine-containing plasmalogens (pPEs) are a unique class of breastmilk (BM) glycerophospholipids containing a vinyl-ether at the sn-1 and a polyunsaturated fatty acid (PUFA) at the sn-2 position of the glycerol moiety. pPEs are present in the milk fat globule membrane, accumulate in the infant brain, and have been implicated in infant...

Maternal body mass index is associated with breast milk (BM) fatty acid composition. This study investigated the effects of BM omega (n)-6:n-3 polyunsaturated fatty acids (PUFAs) from non-obese women and women with obesity on the process of adipogenesis in 3T3-L1 preadipocytes. BM samples were collected from non-obese women (BMNO) and women with ob...

The intestinal microbiota of the preterm neonate has become a major research focus, with evidence emerging that the microbiota influences both short and long-term health outcomes, in the neonatal intensive care unit and beyond. Similar to the term microbiome, the preterm gut microbiome is highly influenced by diet, specifically formula and human mi...

Localized non-inheritable developmental defects of tooth enamel (DDE) are classified as enamel hypoplasia (EH), opacity (OP) and post-eruptive breakdown (PEB) using the Enamel Defects Index. To better understand the etiology of DDE, and in particular possibly modifiable variables, we assessed the linkages amongst exposome variables during the speci...

Storage of human milk and biological implications of free fatty acid.

It is unknown if vitamin D (vitD) sufficiency in breastfeeding mothers can lead to physiological outcomes for their children that are discernible from infant vitD sufficiency per se. In a 3-month, randomized vitD supplementation study of mothers and their exclusively breastfeeding infants, the effects of maternal vitD sufficiency were determined on...

Background: Vitamin D (vitD) plays a major role in maintenance of bone mineral homeostasis. It is unknown if bone mineral content (BMC) and bone mineral density (BMD) differ between infants who receive direct vitD supplementation and those who receive vitD indirectly via their mother's breast milk, while she received a high dose of vitD. It is hypo...

Vitamin D helps the intestine to absorb calcium and other minerals that the body needs, and provides support to the immune system. To carry out these roles, vitamin D must be converted into the active hormone calcitriol (also known as 1,25-dihydroxy-vitamin D). First, vitamin D is metabolized by the liver into a compound called 25(OH)D, which then...

Background: To ensure the safety of higher dose vitamin D supplementation in pregnant and lactating mothers, and urinary calcium/creatinine (UCa/Cr) ratios, serum calcium, and serum 25(OH)D concentrations are closely monitored. To achieve optimal maternal and infant vitamin D status, while avoiding hypercalcemia, safety measures assessing vitD supp...

Vitamin D supplementation during pregnancy has been studied since the early 1980′s and, while many clinical trials have been performed, we remain at a crossroads in our conclusions about vitamin D’s effects during pregnancy and the optimal dose and timing of supplementation [...]

Frozen storage is necessary to preserve expressed human milk for critically ill and very preterm infants. Milk pasteurization is essential for donor milk given to this special population. Due to these storage and processing conditions, subtle changes occur in milk nutrients. These changes may have clinical implications. Potentially, bioactive compl...

Objectives Determine which sociodemographic factors are most associated with increased maternal perceived stress during pregnancy. Evaluate the association between maternal stress and plasma immune-mediator concentrations (IMCs). Methods As part of a prospective, randomized clinical trial, 247 participants completed a Perceived Stress Scale survey...

PurposeTo assess the efficacy of different doses of vitamin D3 on serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone(iPTH), calcium, phosphorus, and alkaline phosphatase concentrations in overweight and obese school-children.MethodsA total of 378 children and adolescents, 6–13 years of age, with age- and sex-specific body mass index(BM...

In preterm infants, the goal of aggressive extrauterine nutritional management is to mimic in utero growth and nutrient accretion. Over the latter half of the 20th century, nutritional optimization through the practice of fortifying human milk rose to practice with increased survival rates in preterm infants of younger gestational age. The quest fo...

This review highlights clinical outcomes of human milk from infancy through adulthood. Human milk outcomes of both preterm and term infants, including critically ill term infants (such as infants with congenital heart disease and those requiring therapeutic hypothermia) are summarized. Several human milk diets are identified to reduce the risk of s...

Little is known about how maternal obesity impacts breast milk (BM) composition and how BM composition may impact growth. We sought to determine the role of maternal body mass index (BMI) on BM inflammatory and oxidative stress markers and to delineate the role of these BM markers on infant growth. This was a secondary analysis of 40 mother-infant...

At no other time during the lifespan is vitamin D status more important than during pregnancy, affecting not only the mother but her growing fetus, and later, her growing infant. While there has been considerable controversy surrounding the daily requirement of vitamin D and what constitutes sufficiency during these critical periods, there is mount...

Vitamin D is an endocrine regulator of calcium and bone metabolism. Yet, its effects include other systems, such as innate and adaptive immunity. Unique to pregnancy, circulating 1,25-dihydroxyvitamin D (1,25[OH]2D) increases early on to concentrations that are 2–3 times prepregnant values. At no other time during the lifecycle is the conversion of...

Objective The goal of this study was to determine if an axis of placental gene expression associated with early onset and severe preeclampsia (EOSPE) was operative in term pregnancy and correlated with vitamin D sufficiency. Methods qPCR analysis of NKX2-5, SAM68, sFLT1 and membrane bound VEGFR1/FLT1 mRNA expression was conducted in placentas from...

Background: The safety of higher dose vitamin D (vitD) supplementation in women who change from exclusive or full breastfeeding to combination feeding or who continue supplementation after cessation of breastfeeding is unknown. Objective: Compare vitD supplementation safety of 6,400 to 400 IU/day and 2,400 IU/day using specific laboratory paramete...

The risk for preeclampsia (PE) is enhanced ~4-fold by the presence of maternal type 1 diabetes (T1DM). Vitamin D is essential for healthy pregnancy. We assessed the total, bioavailable, and free concentrations of plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and vitamin D binding protein (VDBP) at ~12, ~22, and ~32 wee...

For the second aim of the Kellogg Foundation grant, this double-blind RCT investigated the impact of plasma vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) on plasma immune-mediators during pregnancy. We hypothesized that higher 25(OH)D concentrations would associate with reduced pro-inflammatory and increased tolerogenic immune-mediator concent...

Vitamin D could be beneficial for healthy aging in humans. We previously found that vitamin D supplementation may slow down epigenetic aging in young African American adults. We tested new epigenetic clocks developed for neonates among a multiethnic population, and tested the hypothesis that vitamin D supplementation would slow down the epigenetic...

The level of serum 25-hydroxyvitamin D (25(OH)D) at which intact parathyroid hormone (iPTH) is maximally suppressed (suppression point) and below which PTH begins to rise (inflection point) has been used to define optimum 25(OH)D concentration. We aimed to study the association of circulating iPTH with 25(OH)D concentrations and to determine a 25(O...

Aim: The aim of this study was to assess biomarkers of calcium homeostasis and tooth development, in mothers during pregnancy and their children at birth, for enamel hypoplasia (EH) in the primary maxillary central incisor teeth. Methods: Bayesian methodology was used for secondary data analyses from a randomized, controlled trial of prenatal vi...

Vitamin D deficiency has been associated with adverse pregnancy and birth outcomes such as increased risk for preterm birth and preeclampsia. This state of the science review analyzed recently published meta‐analyses and relevant studies that have evaluated the association between vitamin D deficiency and preeclampsia or preterm birth. The results...

Objective Bacterial vaginosis (BV) is associated with vitamin D deficiency and poor pregnancy outcomes. We studied a nested cohort from a randomized controlled trial to investigate the association between BV and vitamin D concentration in pregnancy. Study Design Subjects with randomly assigned 400 versus 4,400 IU of daily cholecalciferol (vitamin D...

Background: International Board Certified Lactation Consultants (IBCLCs) have been in existence for over 3 decades, are currently represented in 110 countries, and have the only internationally recognized certification to provide safe and evidenced-based care for breastfeeding women and their infants. Research aim: To review the literature about...

Objective Evidence supports an inverse association between vitamin D and bacterial vaginosis (BV) during pregnancy. Furthermore, both the vaginal microbiome and vitamin D status correlate with pregnancy outcome. Women of African ancestry are more likely to experience BV, to be vitamin D deficient, and to have certain pregnancy complications. We inv...

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 par...

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 18–45 years with body mass i...

Background: Polymorphic alleles of the vitamin D (vitD)-binding protein (VDBP) gene are associated with discriminatory differences in circulating concentrations of 25-hydroxyvitamin D (25-D), the indicator of vitD status (sufficiency defined by the Endocrine Society as ≥75 nmol/L). Within a diverse group of children, we hypothesized that reaching...

Evidence on the association of vitamin D and parathyroid hormone (PTH) with cardiovascular risk factors in the young is limited. We therefore assessed the relationships of circulating vitamin D and PTH concentrations and subclinical atherosclerosis in overweight or obese children and adolescents. This was a cross-sectional study, investigated the a...

In designing longitudinal lactation research studies, certain factors must be taken into account that are necessary for the generation of meaningful data. Perhaps more like longitudinal childhood research studies in terms of ongoing changes that occur during childhood that challenge study design, longitudinal lactation research studies encompass a...

Pregnancy is a time of tremendous growth and physiological changes for mother and her developing fetus with lifelong implications for the child. The concert of actions that must occur so mother does not reject the foreign tissue of the fetus is substantial. There must be exquisite balance between maternal tolerance to these foreign proteins of pate...

Background: Various natural products are reported to improve maternal milk supply yet are not necessarily safe for infants. Researchers have not systematically studied galactagogue teas for safety. Research Aim: This study evaluates the safety of a galactagogue tea in breastfeeding women and their infants, assessing short- and long-term adverse ef...

Administration of colostrum for early trophic feedings and colostrum oral immune therapy for neonates in the NICU is essential to enhance gut maturation and lower risk of infections. However, it is often difficult for women to collect early colostrum because of its thick viscosity and low volume. Women may be unable to sit upright during pumping se...

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...

Studies have indicated that 25-hydroxyvitamin D (25(OH)D) level in obese is lower than normal weight subjects; however, results of studies that investigated relationship between 25(OH)D and fat mass are inconsistent. In addition, several randomized clinical trials (RCTs) have studied the influence of cholecalciferol supplement on percentage fat mas...

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 desig...

ContextAdult body fat is associated with birth anthropometry, suggesting a role for metabolic regulators including vitamin D and the adipokines—adiponectin and irisin—which have been reported to interact but, as yet, data remain controversial. Objective To study (i) the relationship between vitamin D, its binding protein (VDBP) and the adipokines,...

Pregnancy and lactation both represent a time of rapid bodily change, which include physical proportions, physiology, and responsibility. Arguably, nothing during these times changes more than the requirement and metabolism of vitamin D, although from current Institute of Medicine (IOM) recommendations, one would never surmise this fact. Do the cur...

Objective: To perform per-protocol analysis of data obtained from the NICHD vitamin D pregnancy study published by Hollis et al., which found via intent-to-treat analysis that 4000IU/day vitamin D supplementation is safe and effective in achieving sufficiency in women and neonates. This study hypothesizes that differential adherence as examined by...

Objective: Determine the effect of physical activity on vitamin D (vitD) status in pregnant women.Design/Methods: Women who presented at 10-14 weeks’ gestation participated in vitD supplementation RCT, conducted between November 2012 and June 2016, were randomized into one of two treatment groups: 400 or 4400 IU/day of vitD3. VitD status, as define...

Background: While vitamin D is known to play a role in bone integrity during development, researchers are still investigating its role in body composition. Objective: Determine the interaction of diet, vitamin D status, and ethnicity/race on body composition of 4 to 6 year old children. Study design & methods: A longitudinal follow-up study of 140...

The vitamin D levels in mothers affect the health status of both the mother and breastfeeding infant. Vitamin D deficient mothers’ infants are prone to rickets. While tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has been implicated in cellular growth/apoptosis, immune cell function and bone-resorbing osteoclast formation, the exp...

In this review, we will discuss the changes that occur in the mammary gland from pregnancy to lactation and the issues surrounding the analysis of circulating and milk hormones during the stages of lactogenesis. There is a cascade of events that must occur to achieve milk synthesis, milk ejection, and successful transfer to the breastfeeding infant...

Background: Little is known about bone mineral density (BMD) during pregnancy. Advances in technology with lower radiation emissions by dual-energy X-ray absorptiometry instruments now permit the safe measurement of BMD during pregnancy.Objective: We evaluated maternal BMD during pregnancy as a function of vitamin D status in women of diverse racia...

This critical time frame of intrauterine life development is considered of major importance on the metabolic imprinting of overall health of the offspring, in later life. This requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Dysregulation of these tightly controlled biophenomena...

Pregnancy represents a time of rapid bodily change, which includes physical proportions, physiology and responsibility. At this context, maternal vitamin D stores have been the objective of extensive scientific research during the last decades, focusing on their potential effects on maternal an neonatal health. A growing body of observational studi...

Existing research shows an association between physical activity levels and vitamin D status in the elderly, men, women, children, and adolescent populations. This association has not yet been investigated in postpartum women. We hypothesized that based on the relationship between vitamin D and physical activity found in other populations, greater...

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 pregn...

Background: The extent to which breastfeeding is protective against later-life obesity is controversial. Little is known about differences in infant body composition between breastfed and formulafed infants, which may reflect future obesity risk. Objective: We aimed to assess associations of infant feeding with trajectories of growth and body compo...

Given the high rate of preterm birth (PTB) nationwide and data from RCTs demonstrating risk reduction with vitamin D supplementation, the Medical University of South Carolina (MUSC) implemented a new standard of care for pregnant women to receive vitamin D testing and supplementation.To determine if the reported inverse relationship between materna...

To investigate an immunomodulatory role for vitamin D in pregnancy we used mice raised on vitamin D-sufficient (SUFF), or −deficient (DEF) diets. At embryonic day 14, pregnant mice received intraperitoneal injection of lipopolysaccharide (LPS) or vehicle for 24 hrs, with age-matched non-pregnant mice as controls. In non-pregnant mice, 6 serum analy...

Background: The extent to which breastfeeding is protective against later-life obesity is controversial. Little is known about differences in infant body composition between breastfed and formula-fed infants, which may reflect future obesity risk. Objective: We aimed to assess associations of infant feeding with trajectories of growth and body comp...

Objective: To examine the association between maternal body mass index (BMI) and serum 25-hydroxy vitamin D [25(OH)D] concentration and bone density in mother-infant pairs. Study design: The study was a secondary analysis of 234 exclusively breastfeeding dyads who were recruited in the first postpartum month for a randomized controlled trial of...

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...

PRISMA checklist. (DOC)

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 serv...

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 100nmoles/L, which has pronounced effects on fetal health outcomes. Additionally, associations are noted between low maternal 25(OH)D concentrations and vascular pregnancy...

Background: Vitamin D has neuroprotective and immunomodulatory properties, and deficiency is associated with worse stroke outcomes. Little is known about effects of hypoxia-ischemia or hypothermia treatment on vitamin D status in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized vitamin D metabolism would be dysregulated in neon...