Christina Valentine

Interests

Research

Materna/infant nutrition to prevent morbidities

Teaching

Neonatal physiology, perinatal nutrition

Courses

Scholarly Contributions

Journals/Publications

• Bala, F. E., McGrattan, K. E., Valentine, C. J., & Jadcherla, S. R. (2024). A Narrative Review of Strategies to Optimize Nutrition, Feeding, and Growth among Preterm-Born Infants: Implications for Practice. Advances in nutrition (Bethesda, Md.), 15(11), 100305.
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  Preterm birth is the leading cause of neonatal and under-5 mortality globally, and healthcare-related burden and nutrition-related morbidities are unsustainable, particularly in resource-limited regions. Additionally, preterm infants are susceptible to multiple adverse outcomes including growth faltering, suboptimal neurodevelopment, and multisystemic morbidities. Maturation, healing, repair, and restoration to normalcy in preterm-born infants require optimizing nutrition; only then, prognosis, growth, neurodevelopment, and overall quality of life can improve. In this article, we discuss the various evidence-based feeding and nutritional strategies that can be applicable even in resource-limited settings, where resources and infrastructure for advanced neonatal care are limited. This article addresses nutrition, feeding strategies, and growth monitoring in the neonatal intensive care unit and at discharge to optimize nutrition, growth, and development.
• DeFranco, E. A., Valentine, C. J., Carlson, S. E., Sands, S. A., & Gajewski, B. J. (2024). Racial disparity in efficacy of docosahexaenoic acid supplementation for prevention of preterm birth: secondary analysis from a randomized, double-blind trial. American journal of obstetrics & gynecology MFM, 6(5), 101358.
• Withrow, N. A., Al-Tawil, Y., Patterson, P. J., Wilson, M., Ryan, E., Millovich, V., & Valentine, C. J. (2024). Retrospective Cohort Study Demonstrates Tolerance and Adherence to Pea-Based Complete Enteral Formula When Transitioned from a Previous Hypoallergenic Product. Nutrients, 16(19).
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  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.
• Carlson, S. E., Gajewski, B. J., Valentine, C. J., Sands, S. A., Brown, A. R., Kerling, E. H., Crawford, S. A., Buhimschi, C. S., Weiner, C. P., Cackovic, M., DeFranco, E. A., Mudaranthakam, D. P., & Rogers, L. K. (2023). Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy. Clinical nutrition (Edinburgh, Scotland), 42(2), 235-243.
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  Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed.
• Christifano, D. N., Crawford, S. A., Lee, G., Brown, A. R., Camargo, J. T., Kerling, E. H., Gajewski, B. J., Valentine, C. J., Gustafson, K. M., DeFranco, E. A., & Carlson, S. E. (2023). Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation. Clinical nutrition ESPEN, 53, 93-99.
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  Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (
• Crawford, S. A., Brown, A. R., Teruel Camargo, J., Kerling, E. H., Carlson, S. E., Gajewski, B. J., Sullivan, D. K., & Valentine, C. J. (2023). Micronutrient Gaps and Supplement Use in a Diverse Cohort of Pregnant Women. Nutrients, 15(14).
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  Micronutrition in pregnancy is critical to impact not only fetal growth and development but also long-term physical and psychiatric health outcomes.
• Gajewski, B. J., Carlson, S. E., Brown, A. R., Mudaranthakam, D. P., Kerling, E. H., & Valentine, C. J. (2023). The value of a two-armed Bayesian response adaptive randomization trial. Journal of biopharmaceutical statistics, 33(1), 43-52.
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  We investigate the value of a two-armed Bayesian response adaptive randomization (RAR) design to investigate early preterm birth rates of high versus low dose of docosahexaenoic acid during pregnancy. Unexpectedly, the COVID-19 pandemic forced recruitment to pause at 1100 participants rather than the planned 1355. The difference in power between number of participants at the pause and planned was 87% and 90% respectively. We decided to stop the study. This paper describes how the RAR was used to execute the study. The value of RAR in two-armed studies is quite high and their use in the future is promising.
• Wang, Y., Gajewski, B. J., Valentine, C. J., Crawford, S. A., Brown, A. R., Mudaranthakam, D. P., Camargo, J. T., & Carlson, S. E. (2023). DHA, nutrient intake, and maternal characteristics as predictors of pregnancy outcomes in a randomised clinical trial of DHA supplementation. Clinical nutrition (Edinburgh, Scotland), 42(11), 2229-2240.
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  To investigate the relationships among docosahexaenoic acid (DHA) intake, nutrient intake, and maternal characteristics on pregnancy outcomes in a phase III randomised clinical trial designed to determine the effect of a DHA dose of 1000 mg/day compared to 200 mg/day on early preterm birth (
• Adams, J. M., Valentine, C. J., Karns, R. A., Rogers, L. K., Murase, M., Fowler, G. N., & Nommsen-Rivers, L. A. (2022). DHA Supplementation Attenuates Inflammation-Associated Gene Expression in the Mammary Gland of Lactating Mothers Who Deliver Preterm. The Journal of nutrition, 152(6), 1404-1414.
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  In a randomized trial of DHA supplementation to lactating mothers who delivered preterm, there were significant increases in DHA status in the mother and her infant.
• Crawford, S. A., Christifano, D. N., Kerling, E. H., Gajewski, B. J., Valentine, C. J., Gustafson, K. M., Mathis, N. B., Camargo, J. T., Gibbs, H. D., Sullivan, D. K., Sands, S. A., & Carlson, S. E. (2022). Validation of an abbreviated food frequency questionnaire for estimating DHA intake of pregnant women in the United States. Prostaglandins, leukotrienes, and essential fatty acids, 177, 102398.
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  Docosahexaenoic acid (DHA) intake was estimated in pregnant women between 12- and 20-weeks' gestation using the National Cancer Institute's (NCI) Diet History Questionnaire-II (DHQ-II) and a 7-question screener designed to capture DHA intake (DHA Food Frequency Questionnaire, DHA-FFQ). Results from both methods were compared to red blood cell phospholipid DHA (RBC-DHA) weight percent of total fatty acids. DHA intake from the DHA-FFQ was more highly correlated with RBC-DHA (r=0.528) than the DHQ-II (r=0.352). Moreover, the DHA-FFQ allowed us to obtain reliable intake data from 1355 of 1400 participants. The DHQ-II provided reliable intake for only 847 of 1400, because many participants only partially completed it and it was not validated for Hispanic participants. Maternal age, parity, and socioeconomic status (SES) were also significant predictors of RBC-DHA. When included with estimated intake from the DHA-FFQ, the model accounted for 36% of the variation in RBC-DHA.
• Carlson, S. E., Gajewski, B. J., Valentine, C. J., Kerling, E. H., Weiner, C. P., Cackovic, M., Buhimschi, C. S., Rogers, L. K., Sands, S. A., Brown, A. R., Mudaranthakam, D. P., Crawford, S. A., & DeFranco, E. A. (2021). Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial. EClinicalMedicine, 36, 100905.
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  Several meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (EPB,
• Mudaranthakam, D. P., Brown, A., Kerling, E., Carlson, S. E., Valentine, C. J., & Gajewski, B. (2021). The Successful Synchronized Orchestration of an Investigator-Initiated Multicenter Trial Using a Clinical Trial Management System and Team Approach: Design and Utility Study. JMIR formative research, 5(12), e30368.
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  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.
• Valentine, C. J., Khan, A. Q., Brown, A. R., Sands, S. A., Defranco, E. A., Gajewski, B. J., Carlson, S. E., Reber, K. M., & Rogers, L. K. (2021). Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth. Nutrients, 13(12).
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  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 (
• Valentine, C. J. (2020). Nutrition and the developing brain. Pediatric research, 87(2), 190-191.
• Valentine, C. J., Dingess, K. A., Kleiman, J., Morrow, A. L., & Rogers, L. K. (2019). A Randomized Trial of Maternal Docosahexaenoic Acid Supplementation to Reduce Inflammation in Extremely Preterm Infants. Journal of pediatric gastroenterology and nutrition, 69(3), 388-392.
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  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.
• Copp, K., DeFranco, E. A., Kleiman, J., Rogers, L. K., Morrow, A. L., & Valentine, C. J. (2018). Nutrition Support Team Guide to Maternal Diet for the Human-Milk-Fed Infant. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 33(5), 687-693.
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  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.
• Carlson, S. E., Gajewski, B. J., Valentine, C. J., Rogers, L. K., Weiner, C. P., DeFranco, E. A., & Buhimschi, C. S. (2017). Assessment of DHA on reducing early preterm birth: the ADORE randomized controlled trial protocol. BMC pregnancy and childbirth, 17(1), 62.
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  Preterm birth contributes to 0.5 million deliveries in the United States (one of eight pregnancies) and poses a huge burden on public health with costs in the billions. Of particular concern is that the rate of earliest preterm birth (
• Dingess, K. A., Valentine, C. J., Ollberding, N. J., Davidson, B. S., Woo, J. G., Summer, S., Peng, Y. M., Guerrero, M. L., Ruiz-Palacios, G. M., Ran-Ressler, R. R., McMahon, R. J., Brenna, J. T., & Morrow, A. L. (2017). Branched-chain fatty acid composition of human milk and the impact of maternal diet: the Global Exploration of Human Milk (GEHM) Study. The American journal of clinical nutrition, 105(1), 177-184.
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  An understudied component of the diet, branched-chain fatty acids (BCFAs) are distinctive saturated fatty acids that may have an important influence on health. Human-milk fatty acid composition is known to differ worldwide, but comparative data are lacking on BCFAs.
• Li, Z., Valentine, C. J., Wang, D., Wang, L., & Dong, M. (2017). Comparison of enteral feeding of preterm infants between two hospitals in China and United States. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 30(1), 121-125.
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  To compare the details of preterm infants enteral feeding between the two hospitals in China and in the United States, and to analyze the reason of the differences.
• McNamara, R. K., Vannest, J. J., & Valentine, C. J. (2015). Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology. World journal of psychiatry, 5(1), 15-34.
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  Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with long-standing deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder (ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.
• Merhar, S. L., Meinzen-Derr, J., Sprague, J., Wessel, J. J., Leugers, S., Painter, J., & Valentine, C. J. (2015). Safety and Tolerability of Enteral Protein Supplementation for Infants With Brain Injury. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 30(4), 546-50.
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  We hypothesized that enteral protein supplementation in infants with brain injury would be safe and well tolerated and improve growth.
• Rice, M. S., & Valentine, C. J. (2015). Neonatal Body Composition: Measuring Lean Mass as a Tool to Guide Nutrition Management in the Neonate. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 30(5), 625-32.
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  Neonatal nutrition adequacy is often determined by infant weight gain. The aim of this review is to summarize what is currently known about neonatal body composition and the use of body composition as a measure for adequate neonatal nutrition. Unlike traditional anthropometric measures of height and weight, body composition measurements account for fat vs nonfat mass gains. This provides a more accurate picture of neonatal composition of weight gain. Providing adequate neonatal nutrition in the form of quantity and composition can be a challenge, especially when considering the delicate balance of providing adequate nutrition to preterm infants for catch-up growth. Monitoring weight gain as fat mass and nonfat mass while documenting dietary intake of fat, protein, and carbohydrate in formulas may help provide the medical community the tools to provide optimal nutrition for catch-up growth and for improved neurodevelopmental outcomes. Tracking body composition in term and preterm infants may also provide critical future information concerning the nutritional state of infants who go on to develop future disease such as obesity, hypertension, and hyperlipidemia as adolescents or adults.
• Vanek, V. W., Borum, P., Buchman, A., Fessler, T. A., Howard, L., Shenkin, A., Valentine, C. J., , N. N., & , N. N. (2015). A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 30(4), 559-69.
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  The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) started an intensive review of commercially available parenteral vitamin and trace element (TE) products in 2009. The chief findings were that adult multi-TE products currently available in the United States (U.S.) provide potentially toxic amounts of manganese, copper, and chromium, and neonatal/pediatric multi-TE products provide potentially toxic amounts of manganese and chromium. The multivitamin products appeared safe and effective; however, a separate parenteral vitamin D product is needed for those patients on standard therapy who continue to be vitamin D depleted and are unresponsive to oral supplements. The review process also extended to parenteral choline and carnitine. Although choline and carnitine are not technically vitamins or trace elements, choline is an essential nutrient in all age groups, and carnitine is an essential nutrient in infants, according to the Food and Nutrition Board of the Institute of Medicine. A parenteral choline product needs to be developed and available. Efforts are currently under way to engage the U.S. Food and Drug Administration (FDA) and the parenteral nutrient industry so A.S.P.E.N.'s recommendations can become a commercial reality.
• Li, Z. H., Dong, M., Wang, D. H., & Valentine, C. J. (2014). [Comparison of feeding pattern of preterm infants between two hospitals in China and the United States]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 16(7), 691-5.
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  To compare the feeding pattern of preterm infants between two hospitals in China and the United States.
• Shaikhkhalil, A. K., Curtiss, J., Puthoff, T. D., & Valentine, C. J. (2014). Enteral zinc supplementation and growth in extremely-low-birth-weight infants with chronic lung disease. Journal of pediatric gastroenterology and nutrition, 58(2), 183-7.
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  Zinc deficiency causes growth deficits. Extremely-low-birth-weight (ELBW) infants with chronic lung disease (CLD), also known as bronchopulmonary dysplasia, experience growth failure and are at risk for zinc deficiency. We hypothesized that enteral zinc supplementation would increase weight gain and linear growth.
• Tocco, N. M., Hodge, A. E., Jones, A. A., Wispe, J. R., & Valentine, C. J. (2014). Neonatal therapeutic hypothermia-associated hypomagnesemia during parenteral nutrition therapy. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 29(2), 246-8.
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  Hypoxic-ischemic encephalopathy (HIE) is a significant cause of morbidity and mortality in the neonatal population. Total body cooling in term infants who meet the criteria for moderate to severe HIE has been shown to be neuroprotective. A decreased core body temperature is known to affect kinetic properties of many enzyme systems in which magnesium is a cofactor. Maintenance of magnesium during therapeutic hypothermia appears to play an important role in neuroprotection. Currently, there are no studies evaluating the effects that therapeutic hypothermia in neonates has on serum magnesium levels and implications for parenteral nutrition (PN) management. Our hypothesis was that neonatal hypothermia would result in hypomagnesemia and require magnesium therapy.
• Valentine, C. J., & Schlaudecker, E. P. (2014). 50 years ago in the Journal of Pediatrics: poliomyelitis antibodies in human colostrum and milk. The Journal of pediatrics, 164(1), 82.
• Vanek, V. W., Seidner, D. L., Allen, P., Bistrian, B., Collier, S., Gura, K., Miles, J. M., Valentine, C. J., , N. N., & , A. S. (2014). Update to A.S.P.E.N. position paper: clinical role for alternative intravenous fat emulsions. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 29(6), 841.
• Rogers, L. K., Valentine, C. J., & Keim, S. A. (2013). DHA supplementation: current implications in pregnancy and childhood. Pharmacological research, 70(1), 13-9.
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  Dietary supplementation with ω-3 long chain fatty acids including docosahexaenoic acid (DHA) has increased in popularity in recent years and adequate DHA supplementation during pregnancy and early childhood is of clinical importance. Some evidence has been built for the neuro-cognitive benefits of supplementation with long chain polyunsaturated fatty acids (LCPUFA) such as DHA during pregnancy; however, recent data indicate that the anti-inflammatory properties may be of at least equal significance. Adequate DHA availability in the fetus/infant optimizes brain and retinal maturation in part by influencing neurotransmitter pathways. The anti-inflammatory properties of LCPUFA are largely mediated through modulation of signaling either directly through binding to receptors or through changes in lipid raft formation and receptor presentation. Our goal is to review the current findings on DHA supplementation, specifically in pregnancy and infant neurodevelopment, as a pharmacologic agent with both preventative and therapeutic value. Given the overall benefits of DHA, maternal and infant supplementation may improve neurological outcomes especially in vulernable populations. However, optimal composition of the supplement and dosing and treatment strategies still need to be determined to lend support for routine supplementation.