Christina J. Valentine

Background: Plant-based formulas have become increasingly popular due to their health benefits, environmental concerns, cultural beliefs, improved palatability, and decreased cost. A retrospective chart review of medically stable children transitioning from a hypoallergenic formula to a yellow pea protein plant-based formula (PPPBF) was included. This study aimed to assess gastrointestinal tolerance, weight changes, and adherence to receiving a unique PPPBF. Methods: Healthcare providers (HCPs) from pediatric clinics across the United States who requested increased PPPBF samples between the dates of 1 November 2021and 31 January 2022 and again from 1 February 2022 to 15 April 2022 inputted survey data. The HCPs selected participants based on the inclusion criteria. Results: Seventy-three completed patient surveys were included of children (ages 1–18 years old, 41% females, 59% males). After the transition to PPPBF, 38.4% experienced improvement in GI tolerance, 56.2% experienced no change, and 5.5% reported worsening GI tolerance. There was a 95% adherence rate, and 98.9% reported no adverse reactions or allergic manifestations after formula transition. Conclusions: Transitioning from a hypoallergenic formula to a PPPBF showed a trend toward stable GI tolerance, weight gain or stability, and adherence. A PPPBF offers a first-choice option for children who are on hypoallergenic formulas due to intolerance.

Background: Micronutrition in pregnancy is critical to impact not only fetal growth and development but also long-term physical and psychiatric health outcomes. Objective: Estimate micronutrient intake from food and dietary supplements in a diverse cohort of pregnant women and compare intake to the Dietary Reference Intakes (DRIs). Design: Secondary analysis of women enrolled in a multi-site clinical trial of docosahexaenoic acid (DHA) supplementation who provided their dietary intake using the diet history questionnaire-II (n = 843) or multiple 24 h recalls (n = 178) at baseline and their intake of nutritional supplements at baseline through 30 days postpartum. Participants/Setting: 1021 participants from the parent trial who had reliable data for dietary intake, supplement intake, or both. Main outcome measures: Micronutrient intake from dietary and supplement sources and percentage of intakes meeting the DRIs for pregnancy. Statistical analyses performed: Percent of participants whose intake was below the estimated average requirement (EAR) or adequate intake (AI) and above the tolerable upper limit (UL). Results: Dietary intakes of choline, folate, iron, vitamin D, zinc, vitamin E, magnesium, and potassium, were below the AI or EAR for 30–91% of the participants; thiamin and vitamin B6 were also below the AI or EAR for non-Hispanic/Latina women. Supplement intake improved the intake for most; however, 80% of the group remained below the AI for choline and 52.5% for potassium while 30% remained below the EAR for magnesium. Folate and iron intakes were above the UL for 80% and 19%, respectively. Conclusions: Dietary supplements, despite their variability, allowed the majority of this cohort of pregnant women to achieve adequate intakes for most micronutrients. Choline, magnesium, and potassium were exceptions. Of interest, folate intake was above the tolerable UL for the majority and iron for 16.8% of the participants. Clinicians have the opportunity to address the most common nutrient deficits and limits with advice on food sources that provide choline, magnesium, and potassium and to ensure folate is not overabundant. More research is needed to determine if these findings are similar in a cross-sectional population.

Background: As the cost of clinical trials continues to rise, novel approaches are required to ensure ethical allocation of resources. Multisite trials have been increasingly utilized in phase 1 trials for rare diseases and in phase 2 and 3 trials to meet accrual needs. The benefits of multisite trials include easier patient recruitment, expanded generalizability, and more robust statistical analyses. However, there are several problems more likely to arise in multisite trials, including accrual inequality, protocol nonadherence, data entry mistakes, and data integration difficulties. Objective: The Biostatistics & Data Science department at the University of Kansas Medical Center developed a clinical trial management system (comprehensive research information system [CRIS]) specifically designed to streamline multisite clinical trial management. Methods: A National Institute of Child Health and Human Development-funded phase 3 trial, the ADORE (assessment of docosahexaenoic acid [DHA] on reducing early preterm birth) trial fully utilized CRIS to provide automated accrual reports, centralize data capture, automate trial completion reports, and streamline data harmonization. Results: Using the ADORE trial as an example, we describe the utility of CRIS in database design, regulatory compliance, training standardization, study management, and automated reporting. Our goal is to continue to build a CRIS through use in subsequent multisite trials. Reports generated to suit the needs of future studies will be available as templates. Conclusions: The implementation of similar tools and systems could provide significant cost-saving and operational benefit to multisite trials.

Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks’ gestation) and preterm birth (less than 37 weeks’ gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12–20 weeks’ gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1β, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: As the cost of clinical trials continues to rise, novel approaches are required to ensure ethical allocation of resources. Multisite trials have been increasingly utilized in phase 1 trials for rare diseases and in phase 2 and 3 trials to meet accrual needs. The benefits of multisite trials include easier patient recruitment, expanded generalizability, and more robust statistical analyses. However, there are several problems more likely to arise in multisite trials, including accrual inequality, protocol nonadherence, data entry mistakes, and data integration difficulties. Objective: The Biostatistics & Data Science department at the University of Kansas Medical Center developed a clinical trial management system (comprehensive research information system [CRIS]) specifically designed to streamline multisite clinical trial management. Methods: A National Institute of Child Health and Human Development–funded phase 3 trial, the ADORE (assessment of docosahexaenoic acid [DHA] on reducing early preterm birth) trial fully utilized CRIS to provide automated accrual reports, centralize data capture, automate trial completion reports, and streamline data harmonization. Results: Using the ADORE trial as an example, we describe the utility of CRIS in database design, regulatory compliance, training standardization, study management, and automated reporting. Our goal is to continue to build a CRIS through use in subsequent multisite trials. Reports generated to suit the needs of future studies will be available as templates. Conclusions: The implementation of similar tools and systems could provide significant cost-saving and operational benefit to multisite trials. Trial Registration: ClinicalTrials.gov NCT02626299; https://tinyurl.com/j6erphcj

Maternal supplementation with 1000 mg/day docosahexaenoic acid (DHA) provides third trimester DHA accretion levels in breast milk for the preterm infant. We hypothesized that DHA supplementation to mothers providing breastmilk for extremely preterm infants would result in decreased inflammatory markers, in the infant. Mother/infant dyads (n = 27) were enrolled at birth and mothers were assigned to receive 200 or 1000 mg/day of DHA. Milk and plasma samples were analyzed for fatty acids and inflammatory markers. Decreases in inflammation were observed in both maternal and infant plasma and correlated with red blood cell (RBC) DHA levels. The fact that maternal DHA supplementation decreases infant markers of inflammation implies that DHA, delivered through breastmilk, has the potential to decrease inflammation in the infant.

Background: Human milk feeding is encouraged for all infants; however, the mammary gland depends on maternal dietary intake of vitamins A, B1, B2, B6, B12, D, docosahexaenoic acid (DHA), choline, and iodine. Nutrition support team knowledge of maternal feeding guidelines for these nutrient sources can therefore impact infant intake. We hypothesized that these key nutrients for lactation in the mother's diet would be less than the dietary guidelines in the United States.Methods: This was a secondary analysis of nutrition data collected during a randomized, controlled trial. Dietary records were analyzed from 16 mothers (13 with singleton and 3 with multiple births) completing the study. Mean dietary intakes of selected nutrients were calculated and compared with the current dietary reference intakes.Results: Mean maternal dietary intake for singletons was significantly (P < .05) lower than the dietary reference intakes for (vitamin A (58%), vitamin D (44%), and choline (58%);) DHA comprised only 5% of the current expert recommendation. Based on singleton recommendations, mothers to twins consumed an adequate intake except for DHA.Conclusions: Women providing breast milk for singleton preterm infants did not consume dietary reference intakes for key nutrients. Twin mothers’ diets were adequate except for DHA, but these guidelines are based on singleton pregnancies and remain poorly understood for twin needs. The nutrition support team can have a unique role in maternal dietary education to impact human milk nutrient delivery to the infant.