Progress 07/15/09 to 01/14/11
Outputs
OUTPUTS: Project # 1: To determine effect of varied maternal choline intake on biomarkers of maternal and fetal status. (Caudill) Completed activities include: menu development, measurement of choline and folate content; screening and recruiting of study participants; feeding trials; measurement of choline and its metabolites in blood, urine and placental tissue at multiple time points; and performing the cognitive tests in the infants. Statistical analyses have been conducted and manuscript writing is underway. Dissemination to communities of interest includes: 1)Choline supplementation of the maternal diet alters metabolomic profiles and gene expression. Canadian Nutrition Society Conference; 2)Pre and Postnatal Health: Evidence of an Increased Choline Requirement. Nutrition Educators from Cornell Cooperative Extension; 3)Genetic variation in methyl metabolizing enzymes, impact on folate (and choline) bioavailability. UC Davis Bioavailability Conference; 4)Pre and Postnatal Health: Evidence of an Increased Choline Requirement. National WIC Conference; Nutrition and Breastfeeding Conference; 5)Pre and Postnatal Health: Evidence of an Increased Choline Requirement. 55th American College of Nurse-Midwives Annual Meeting & Exposition; 6) Pre and Postnatal Health: Evidence of an Increased Choline Requirement. Nutrition Adventure, National Cattlemen's Beef Association; 7) Pre and Postnatal Health: Evidence of an Increased Choline Requirement. Choline Science Summit. USDA, Economic Research Service; 8) Choline and its relation to fetal development. Florida Dietetic Association Annual Meeting. Project # 2: To assess the impact of maternal calcium intake and vitamin D status during pregnancy on longitudinal changes in maternal bone mass and fetal bone growth. (O'Brien) Ca and vitamin D status were assessed longitudinally in a cohort of 171 pregnant adolescents (13.6 - 18.7 y of age). Over 65% of this group was African American and 24% were Hispanic. Maternal and neonatal hormonal status, infant birth weight, birth length, fetal bone growth and placental expression of proteins involved in mineral transport were examined. Research presentations and laboratory tours were provided to freshmen minority biology students to encourage students to become involved in human metabolic research. Outreach activities included research seminars at the University of Rochester and Yale University. Results have been disseminated at national meetings such as: American Society of Bone and Mineral Research, Developmental Origins of Health and Disease, Experimental Biology and The Society for Gynecological Investigation. Two doctoral students are working on their dissertation using samples generated from this study and two others have been involved in side projects utilizing samples obtained from this study. Project # 3: Evaluation of enzyme activity of common genetic variants of cytochrome P450-4F. A series of investigations was performed to clarify the role of cytochrome P450-4F2 in metabolism and bioavailability of vitamin E and vitamin K. Results have been presented at the 2010 Experimental Biology meetings in Anaheim, CA. One PhD dissertation has been provided. PARTICIPANTS: Participants: Patrick Stover, PhD, PI Marie Caudill, PhD, Co-Investigator Kimberly O'Brien, PhD, Co-investigator Robert Parker, PhD, Co-Investigator Project #1: Partner Organizations: Cayuga Medical Center, Ithaca, NY. Collaborators: Eva Pressman, MD - University of Rochester School of Medicine Srisatish Devapatla, MD- Cayuga Medical Center, Ithaca, NY Training: Cydne Perry - Postdoctoral Associate Jian Yian- Predoctoral Student Xinyin Jiang- Predoctoral Student Allyson West - Predoctoral Student 20 undergraduate nutrition majors participated in the execution of this project. Students were trained on various aspects of conducting clinical research in human study participants. Project #2: Partner Organizations: University of Rochester School of Medicine Role: 1) Provided access to patient population and regulatory infrastructure necessary to oversee human research regulations. 2) Provided office space for health project coordinator who oversaw the implementation of the study. Collaborators: Eva Pressman, MD - University of Rochester School of Medicine Thomas McNanley, MD - University of Rochester School of Medicine Elizabeth Cooper, CNM, EdD - University of Rochester School of Medicine Training: Bridget Essley: Predoctoral Student: Working on project for doctoral research Katie Hootman: Predoctoral Student: Working on study for subproject Chang Cao: Predoctoral Student: Working on project samples for doctoral research Sunmin Lee: Predoctoral Student: Working on project samples for doctoral research Marisa Foehr, PhD, Postdoctoral Fellow Project # 3: Collaborators: David Stec, University of Mississippi Medical Center, Jackson, MS Training: Sabrina Bardowell, Predoctoral student. Thesis research Several undergraduate nutrition majors participated in the project. TARGET AUDIENCES: Target Audiences: Project # 1: The target audience is pregnant women, nutritionists and clinicians Project # 2: The proposed studies and data generated have targeted several of the research gaps on calcium and vitamin D homeostasis during pregnancy that were identified by the 2010 IOM Committee on Calcium and Vitamin D. Data generated from our study will further our understanding of the functions and mechanisms of regulation of calcium and vitamin D during the reproductive period and the impact of maternal status on neonatal status at birth. Our findings from this racially diverse, pediatric population provide novel data relevant to minority health and maternal /neonatal outcomes. These results are relevant to adult and adolescent pregnant women throughout the United States and can be used to better inform policy for public health benefit. The increased infrastructure that has occurred as a result of this funding will also provide a subsequent foundation for the training of research professionals in issues relevant to the food supply in relation to optimal human health and nutrition. Parker (Project 3): General applicability. Potential implications for patients on anticoagulant therapy. Project Modifications No Project Modifications PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Project # 1: A maternal choline intake exceeding current recommendations yielded higher concentrations of choline metabolites in maternal blood, placental tissue and cord blood. Pregnancy affected choline metabolism with pregnant women having higher plasma free choline but 50% lower plasma betaine and dimethylglycine. Cognitive testing in the infants of the women participating in this choline intervention study is complete. Statistical analysis is underway. Project # 2: In these teens, 9% of babies were born prematurely and low birth weight was present in 6% of the babies born to this age group. Of concern, over 3% of these pregnancies ended in fetal death in utero. Average calcium intake in these adolescents was suboptimal; only 29 % of teens met the current EAR (1100 mg/d) and 16% consumed the current RDA for calcium (1300 mg/day). Roughly 50% of teens were vitamin D insufficient (25(OH)D ≤ 20 ng/mL), with minority participants having a higher prevalence of insufficiency than Caucasians at all time points. Maternal D status was significantly related to neonatal D status putting >50% of these neonates at risk for suboptimal bone growth and development. Maternal vitamin D insufficiency was also found to have a significant negative impact on fetal bone growth. Infants with sufficient levels of vitamin D at birth had higher birth weight, head circumference, and biparietal diameter Z-scores and longer femur and humerus length Z scores. In these adolescents a net loss of maternal bone was evident at the heel over the course of pregnancy. This loss appeared to be higher in those with vitamin D insufficiency. Findings generated to date speak to the need for research on Ca and D supplementation in this age group to assess the ability of supplementation to attenuate the adverse effects observed. Efforts are also needed to manage the excessive gestational weight gains that are common across pregnancy in this pediatric population and that exacerbate deficiencies of nutrients such as vitamin D and iron. Project # 3: (a) Two enzyme variants of cytochrome P450-4F2 were measured using several dietary forms of vitamin E. The results suggest that individuals carrying these mutations may exhibit altered vitamin E status such that dietary alterations may be recommended.
Publications
- Essley BV, McNanley T, Cooper EM, McIntyre AW, Witter F, Harris ZL, O'Brien KO. 2011. Osteoprotegerin differs by race and is related to infant birth weight z-score in pregnant adolescents. Bone.
- Abstracts: Essley BV, Cooper E, McNanley T, McIntyre AW, Kent T, Witter F, Harris ZL. 2011. Maternal Weight Gain is Associated with Birth Weight Z Score, LBW and Preterm Birth in Pregnant Adolescents. Society for Gynecological Investigation; [S-279]
- Essley BV, McIntyre AW, Cooper E, McNanley T, Kent T, Witter FR, Harris ZL, O'Brien KO. 2010. Increases in PTH and serum NTX are Associated with Maternal Bone Loss in Pregnant Adolescents. J Bone Miner Res. 25 (Suppl 1).
- Bardowell SA, Stec DE and Parker RS. 2010. Common variants of cytochrome P450 4F2 exhibit altered vitamin E -omega-hydroxylase specific activity. J Nutrition 140:1901-1906. Bardowell, SA, Stec, DE, Parker, RS. 2010. Two common variants in the human CYP4F2 gene result in substantial alterations in vitamin E-ω-hydroxylase specific activity. FASEB J. 24, 552.2.
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Progress 07/15/09 to 07/14/10
Outputs
OUTPUTS: Project 1: To determine effect of maternal choline intake on biomarkers of maternal and fetal choline status. Markers of DNA integrity/damage in lymphocytes from pregnant and nonpregnant women consuming two doses of choline intake (450 vs 900 mg/d) as well as in placental tissue from the pregnant study participants were examined. Inflammatory markers were also assessed. Specific Aim 1: Progress made includes measurements of plasma IL-1B, IL-6, TNF-alpha, NF-kB, and CRP in 20 pregnant and 20 nonpregnant women. Specific Aim 2: Progress made includes genome-wide analysis of gene expression in placental tissue obtained from 20 women (10 on 450 and 10 on 900 mg/d). Preliminary data show that the expression of 79 genes in placental tissue were differentially affected (P<0.01, fold change > 2.0) by maternal choline intake including genes involved in DNA and histone methylation and the preeclampsia risk factor, soluble fms-like tyrosine kinase 1 (sFlt-1). In addition, we have identified numerous biological processes impacted by maternal choline intake. Specific Aim 3: Progress made includes analyzing DNA strand breaks by the Comet assay in circulating lymphocytes obtained from pregnant (n=20) versus nonpregnant (n=20). Preliminary results show greater levels of lymphocyte DNA damage in pregnant women compared to nonpregnant control women. Project 2: To assess the impact of maternal calcium intake and vitamin D status during pregnancy on longitudinal changes in maternal bone mass and fetal bone growth and maternal and fetal calcitropic hormone status. Longitudinal studies were completed in 220 pregnant adolescents. These studies showed that vitamin D insufficiency is prevalent among pregnant adolescents. Maternal vitamin D status was related to vitamin D status in neonates. A relationship between maternal vitamin D status and infant birth weight was seen. Maternal leptin concentration, race, and season were significant predictors of maternal vitamin D status. Maternal vitamin D insufficiency had a negative impact on fetal bone growth. Fetal femur length z-scores are shorter in adolescents with suboptimal vitamin D status. Markers of bone formation (osteocalcin) and bone resorption (serum N-telopeptide) were also found to increase across gestation. OPG, a bone-protective protein also increases significantly in maternal circulation from mid-gestation to delivery. These data on OPG are the first to our knowledge to be reported in a cohort of pregnant adolescents. In these adolescents serum hepcidin at mid-gestation averaged 32.1 +/- 28.3 ng/mL (n=93) a value that was approximately 4-fold lower than that measured among their neonates at birth (133.6 +/- 100.2 ng/mL, n=100). These data indicate that the fetal liver is regulating production of this hormone in response to fetal iron demands and not in response to maternal iron stores. Adolescents with higher iron stores had a significantly higher serum hepcidin concentration during mid-gestation. Higher concentrations of hepcidin limit iron absorption in teens that are iron replete. PARTICIPANTS: This research enabled the training of seven doctoral students in the Graduate Field of Nutrition at Cornell University. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Restructuring the wholesomeness of the food supply, and promoting healthy dietary habits and physical activity, increasingly are identified by the USDA as major public health objectives to secure longer lives and better quality of living throughout the life cycle. To achieve these goals, dietary recommendations must be increasingly grounded in an understanding of human nutrient dynamics and thereby result in more accurate and scientifically informed nutrition and agriculture policies for public health benefit. The results described above from new human metabolic studies address the role of calcium and choline nutrition in human health. The proposed studies use of state-of-the-art stable isotope approaches to understand human nutrient dynamics at the whole body and cellular level in healthy humans. The research completed demonstrates that: 1) choline consumption at intakes higher than the recommended amounts improves maternal and fetal biomarkers of choline status; 2) pregnancy alters biomarkers of choline status; 3) prenatal maternal choline intake may improve infant cognitive function in study participants consuming controlled choline intakes of 450 or 900 mg/d; 4) maternal Ca intake and vitamin D status affects maternal bone loss and fetal bone growth during pregnancy; and 5) maternal Ca intake and vitamin D status during pregnancy influences bone mineral content and relationships between maternal and neonatal calcitropic status at parturition. Data from the proposed studies have targeted several of the research recommendations that were raised by the 2001 Institute of Medicine's Dietary Reference Intakes for iron including; "Study of the effect of limited iron intake during pregnancy on infant iron status during the first 6 months of life" and "integrative mechanisms of iron transporter proteins that influence absorption in various dietary conditions and physiological states". Results from these studies will have relevance to the larger population of pregnant women in the United States and will further our understanding of the functions and mechanisms of regulation of choline, calcium, vitamin D and iron homeostasis during the reproductive period.
Publications
- Bardowell SA, Stec DE and Parker RS. 2010. Common variants of cytochrome P450 4F2 exhibit altered vitamin E omega-hydroxylase specific activity. J Nutrition (2010, in press)
- Young MF, Pressman E, Foehr M, McNanley T, Cooper E, Guillet R, Orlando M, McIntyre A, Lafond J, O'Brien KO. Impact of Maternal Iron Status on Placental Transferrin Receptor Expression. Placenta 2010 in press.
- Jaacks LM, Young MF, Essley BV, McNanley TJ, Cooper EM, Pressman EK, McIntyre AW, Orlando MS, Abkowitz JL, Guillet R, OBrien KO. Expression of the Heme Transporters, Feline Leukemia Virus Subgroup C Receptor (FLVCR), and Breast Cancer Resistance Protein (BCRP) in the Placenta in Relation to Maternal and Neonatal Iron Status in Pregnant Adolescents. Submitted 2010
- Essley BV, McNanley T, Cooper E, McIntyre A, Kent T, Foehr M, Witter F, Harris Z, OBrien KO. Markers of Bone Turnover, Osteoprotegerin (OPG), and Vitamin D across Gestation in Pregnant Adolescents. FASEB J. 2010 24:917.11
- Jaacks LM, Young MF, Essley BV, McNanley TJ, Cooper EM, Pressman E, McIntyre AW, Orlando MS, Abkowitz JL, Guillet R, OBrien KO. Maternal and Neonatal Iron Status Impact the Expression of the Heme Transporter, FLVCR, in the Placenta. FASEB J. 2010 24:208.6
- OBrien KO, Essley BV, Young MF, Foehr M, Cooper B, Pressman E, Harris, Witter F, McIntyre A, McNanley T. Fetal bone growth in pregnant adolescents is associated with maternal vitamin D status. J Dev Origins of Health and Disease 2009; 1(1): S47. Essley B, Foehr M, Cooper E, McIntyre A, Kent T, McNanley T, Witter F, Harris Z, Lafond J, OBrien K. Parathyroid hormone (PTH) values, Vitamin D status, Fetal Bone Growth, and Placental RANK-L expression among Pregnant Adolescents. FASEB J 2009; 23:731.5.
- Essley B, Foehr M, Cooper E, McIntyre A, Kent T, McNanley T, Witter F, Harris Z, Lafond J, OBrien K. Parathyroid hormone (PTH) values, Vitamin D status, Fetal Bone Growth, and Placental RANK-L expression among Pregnant Adolescents. FASEB J 2009;23:731.5.
- Young M, Foehr M, McNanley T, Cooper E, Pressman E, Guillet R, Orlando M, McIntyre A, Lafond J, OBrien KO. Role of Maternal/Fetal Iron Status on Placental Transferrin Receptor Expression. FASEB J. 2009; 23:105.7. OBrien KO, Pressman E, McNanley T, Cooper E, McIntyre A, Orlando M, Guillet R. Impact of maternal anemia on neonatal iron status, placental iron transport and functional outcomes at birth among pregnant adolescents. 2009 International Food Technology meeting; Anaheim, CA. Submitted; December 2008.
- Caudill MA. Pre- and Postnatal Health: Evidence of Increased Choline Needs. J Am Diet Assc. 2010;110:1198-1206.
- Caudill MA. Folate bioavailability: Implications for establishing dietary recommendations and optimizing status. Am J Clin Nutr 2010;91(suppl):1455S-60S. doi: 10.3945/ajcn.2010.28674E.
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