Progress 07/01/02 to 06/30/06
Outputs
Oral cleft birth defects (cleft lip and cleft palate) are among the most common congenital malformations, occur at high levels in the Philippines, and have been linked to poor maternal nutrition. Our studies of biochemical indicators of maternal nutritional status in the Philippines have provided evidence that poor folate, vitamin B-6, and zinc status are associated with an increased risk of oral clefts. Objective 1 included organizational activities in the Philippines to support nutrition-based studies. We conducted a case-control study in Cebu Province, Central Philippines, in May 2003 and found that maternal zinc deficiency is widespread and strongly associated with risk of oral clefts. Our previous studies found evidence that folate and vitamin B-6 status were associated with cleft risk. While we were able to organize relatively short-term field studies using case-control study designs, limitations in funding and local infrastructure hindered the development of
larger-scale vitamin supplementation trials. Objective 2 included development of geographical information systems (GIS) for the support of epidemiologic field work in the Philippines. We purchased a copy of the Philippine Digital Atlas (PDA) from Geodata Systems Technologies, Inc. (Manila) which has digitized boundaries of all of the 43,000 barangays (smallest government units) of the Philippines. We have been able use the barangay map data to generate maps of our 2003 field sites in our Cebu study and after extensive sampling of other sites in this data base have developed a comprehensive resource for mapping data in all of the 43,000 barangays in the Philippines that will be useful for further projects in nutrition, agriculture, health, and international development. We were not able to find barangay-level demographic and health data for linkage to the Philippines PDA during this project but we remain optimistic that future studies will be able to build upon these mapping resources.
Objective 3 included linking and expanding oral cleft registries in five geographic areas of the Philippines. Limited funding and lack of local infrastructure were serious obstacles to registry development for vitamin supplementation trials. In response we submitted a grant proposal to the U.S. National Institutes of Health with the aim of expanding cleft studies in the Philippines as well as in China, Taiwan, and Singapore. Because of the present difficulties and high costs of conducting trials (Objective 4) we suggest that as an alternative additional observational studies of folate, B-6, and zinc status in relation to oral clefts be conducted in the Asia region. Dr. Munger is a consultant to an Asia regional oral cleft genetics project and helped organize a World Health Organization meeting on International Collaborative Studies of Craniofacial Anomalies. These developments have led us to seek funding for a broader regional approach to studying nutrition and oral clefts, rather
than relying solely on a vitamin supplementation trial in the Philippines.
Impacts
This research has identified folate, B-6, and zinc to be associated with cleft lip and palate birth defects in the Phillipines. Their supplementation may be important in the prevention of oral cleft birth defects, though future research is needed.
Publications
- Little, J., A. Cardy, Munger, R.G. 2004. Tobacco smoking and oral clefts: a meta-analysis. Bull World Health Organ 82(3): 213-8.
- Munger, R.G., Sauberlich, H.E., Corcoran, C., Nepomuceno, B., Daack-Hirsch, S., Solon, F.S. 2004. Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in the Philippines. Birth Defects Research Part A: Clinical and Molecular Teratology. 70(7): 464-71.
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Progress 01/01/05 to 12/31/05
Outputs
Oral cleft birth defects (cleft lip and cleft palate) are among the most common congenital malformations, occur at high levels in the Philippines, and have been linked to poor maternal nutrition. Our studies of biochemical indicators of maternal nutritional status in the Philippines have provided evidence that poor folate, vitamin B-6, and zinc status are associated with an increased risk of oral clefts. Objective 1 included organizational activities in the Philippines to support nutrition-based studies. We conducted a case-control study in Cebu Province, Central Philippines, in May 2003 and found that maternal zinc deficiency is widespread and strongly associated with risk of oral clefts. Our previous studies found evidence that folate and vitamin B-6 status were associated with cleft risk. While we were able to organize relatively short-term field studies using case-control study designs, limitations in funding and local infrastructure hindered the development of
larger-scale vitamin supplementation trials. Objective 2 included development of geographical information systems (GIS) for the support of epidemiologic field work in the Philippines. We purchased a copy of the Philippine Digital Atlas (PDA) from Geodata Systems Technologies, Inc. (Manila) which has digitized boundaries of all of the 43,000 barangays (smallest government units) of the Philippines. We have been able use the barangay map data to generate maps of our 2003 field sites in our Cebu study and after extensive sampling of other sites in this data base have developed a comprehensive resource for mapping data in all of the 43,000 barangays in the Philippines that will be useful for further projects in nutrition, agriculture, health, and international development. We were not able to find barangay-level demographic and health data for linkage to the Philippines PDA during this project but we remain optimistic that future studies will be able to build upon these mapping resources.
Objective 3 included linking and expanding oral cleft registries in five geographic areas of the Philippines. Limited funding and lack of local infrastructure were serious obstacles to registry development for vitamin supplementation trials. In response we submitted a grant proposal to the U.S. National Institutes of Health with the aim of expanding cleft studies in the Philippines as well as in China, Taiwan, and Singapore. Because of the present difficulties and high costs of conducting trials (Objective 4) we suggest that as an alternative additional observational studies of folate, B-6, and zinc status in relation to oral clefts be conducted in the Asia region. Dr. Munger is a consultant to an Asia regional oral cleft genetics project (Dr. Terri Beaty, Principal Investigator, Johns Hopkins University) and helped to organize a World Health Organization meeting on International Collaborative Studies of Craniofacial Anomalies held in Geneva in December, 2004; these developments have
led us to seek funding for a broader regional approach to studying nutrition and oral clefts, rather than relying solely on a vitamin supplementation trial in the Philippines.
Impacts
Three nutrients have been found to be associated with cleft lip and palate birth defects in the Philippines including folate, vitamin B-6, and zinc. These vitamin deficiencies are common among mothers in the Philippines and may be important in the prevention of oral cleft birth defects. Vitamin supplementation trials are needed to establish a firm causal link between these nutrients and oral clefts.
Publications
- Tamura, T.. Munger R. G., Corcoran, C., Bacayao, J. Y., Nepomuceno, B., Solon, F. (2005). "Plasma zinc concentrations of mothers and the risk of nonsyndromic oral clefts in their children: A case-control study in the Philippines." Birth Defects Res A Clin Mol Teratol 73(9): 612-6.
- Munger, R.G. (2002) The prevention of craniofacial anomalies. In: Global Strategies to Reduce the Health-Care Burden of Craniofacial Anomalies. Report of WHO meetings on International Collaborative Research on Craniofacial Anomalies. World Health Organization. Geneva.
- Mitchell, L. E., Beaty, T. H., Lidral, A. C., Munger, R. G., Murray, J. C., Saal, H. M., Wyszynski, D. F. Guidelines for the design and analysis of studies on nonsyndromic cleft lip and cleft palate in humans: summary report from a workshop of the international consortium for oral clefts genetics. Cleft Palate Craniofac J. 2002;39(1):93-100.
- Munger, R. (2002). Maternal nutrition and oral clefts. In: Cleft Lip and Palate: from Origin to Treatment. D. Wyzsynski., Editor. Oxford University Press. New York.
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Progress 01/01/04 to 12/31/04
Outputs
Objective 1 includes organizational activities in the Philippines to support a nutrition-based oral cleft prevention trial. Data collected in Cebu Province, Central Philippines, were analyzed and evidence was found that maternal zinc deficiency is widespread in the Philippines and strongly associated with risk of oral clefts. Our studies have thus found three nutrients that are candidates for a maternal nutritional supplementation trial: zinc, folate, and vitamin B-6. Dr. Munger met with Dr. Carmencita Padilla, Director of the UPM Cleft Registry in December and hosted a visit to the USU campus by UPM computer programmer, Mr. Meiller Manguiat in November. Objective 2 includes development of geographical information systems (GIS) in collaboration with the USU Remote Sensing-GIS Center. Mr. Samson Gebreab continues to work as a graduate research assistant and we have shifted our efforts from digitizing paper maps to work with newly available digital map files. We
purchased a copy of the Philippine Digital Atlas (PDA) from Geodata Systems Technologies, Inc. (Manila) which has digitized boundaries of all of the 43,000 barangays (smallest government units) of the Philippines. Funding for Mr. Gebreabs assistantship and the PDA was provided by the USU Center for Epidemiologic Studies. Mr. Gebreab has worked with Mr. Manguiat in linking the PDA map files to data we have obtained in our oral cleft studies using ArcGIS software. The detailed digital mapping of all local government units that we have from the Philippines is not available in other developing countries that we are aware of and provide a unique resource for developing further projects in nutrition, agriculture, health, and international development. We are now searching for additional health and demographic data to link to the Philippines PDA. Objective 3 includes linking and expanding oral cleft registries in five geographic areas of the Philippines. The most promising efforts are being
led by Dr. Padilla in the metropolitan Manila area and we have assisted in the review of data collection forms and data management procedures. Limited funding remains a serious obstacle to registry development elsewhere in the Philippines. In response to this situation (and as a part of Objective 4, seeking external funding) we submitted a grant proposal to the U.S. National Institutes of Health on 1 October 2004 entitled Nutrition and Oral Clefts in Asia: Planning grant with the aim of expanding cleft studies in the Philippines as well as in China, Taiwan, and Singapore. Dr. Munger is a consultant to an Asia regional oral cleft genetics project (Dr. Terri Beaty, Principal Investigator, Johns Hopkins University) and Dr. Munger helped to organize a WHO meeting on International Collaborative Studies of Craniofacial Anomalies held in Geneva in December, 2004; these developments have led us to seek funding for a broader regional approach to studying nutrition and oral clefts, rather than
relying solely on the Philippines.
Impacts
Poor maternal zinc nutriture was found to be widespread in the Philippines and significantly associated with the risk of oral cleft birth defects. Our previous studies have found that maternal folate and vitamin B-6 status may be implicated in oral clefts in the Philippines. A geographical information system is being developed to integrate nutritional, agricultural, and health information in the Philippines. Mapping the occurrence of nutritional deficiencies and the occurrence of birth defects may lead to effective public health programs to improve nutrition and prevent birth defects in the Philippines and elsewhere.
Publications
- Bastian L.A., West N.A., Corcoran C., Munger R.G. (2005). Number of children and the risk of obesity in older women. Preventive Medicine. 40:99-104.
- Hayden KM, Pieper CF, Welsh-Bohmer KA, Breitner JCS, Norton MC, Munger RG. (2004). "Self- or proxy-reported stroke and the risk of Alzheimer disease." Arch Neurol 61(6): 982.
- Wengreen HJ, Munger RG, West NA, Cutler DR, Corcoran CD, Zhang J, Sassano NE. (2004) Dietary protein intake and risk of osteoporotic hip fracture in elderly residents of Utah. Journal of Bone and Mineral Research. 19(4): 537-45.
- Little, J., A. Cardy, Munger, R.G. (2004). "Tobacco smoking and oral clefts: a meta-analysis." Bull World Health Organ 82(3): 213-8.
- Munger RG, Sauberlich HE, Corcoran C, Nepomuceno B, Daack-Hirsch S, Solon FS. (2004) Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in the Philippines. Birth Defects Research Part A: Clinical and Molecular Teratology. 70(7): 464-71.
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Progress 01/01/03 to 12/31/03
Outputs
Objective 1 includes organizational activities in the Philippines to support a full-scale oral cleft prevention trial. In May, 2003, conducted two weeks of fieldwork in Cebu province of the central Philippines. Health and nutrition surveys were conducted in nine barangays (smallest local unit of government). Blood specimens were collected, rapidly processed, and transported to the laboratory at the University of Alabama. Visited the National Center for Maternal and Infant Health at Peking University Health Science Center, Beijing, China, to consult on the extensive birth defects surveillance system in China. Toured rural and urban clinics and hospitals participating in the surveillance system and the data management center. Objective 2 includes development of geographical information systems (GIS) data in collaboration with the USU Remote Sensing-GIS Center. Cataloged 33 high-resolution paper maps of the Metropolitan Manila area obtained last year and created a
reference grid of all the maps. Tested scanning and digitizing methods to create map layers with images and municipal and provincial boundaries. Creating an ArcView database with reference points from each of the separate maps and working on projection methods so that data from the 33 separate maps can be displayed seamlessly. Conducted internet searches for digital map resources of the Philippines and have received price quotes from Geodata Systems Technologies, Inc. for data bases that include barangay boundaries with data from the 2000 Philippines census; the cost of the data base is prohibitive and we are exploring options to see if we can collaborate with universities or government institutions in the Philippines obtaining access to these data bases for health-related research. Investigating sources of satellite images for additional map layers. Objective 3 includes linking and expanding oral cleft registries in five geographic areas of the Philippines. Our work is still at the
preliminary stage with focus on Cebu province and the Metropolitan Manila area. Our May 2003 field survey included collection of data on the willingness of mothers to participate in a oral cleft prevention study and involvement of barangay health workers.
Impacts
Collaboration with the successful birth defects surveillance program in China will allow us to draw on their experience and expertise in establishing similar research efforts in the Philippines. The development of digital mapping systems for the Philippines vital statistics and birth defects data will allow sophisticated approaches to data analyses and display.
Publications
- Cardy, A., Little, J., and Munger, R.G. 2004. Tobacco smoking and oral clefts: a meta-analysis. Bulletin of the World Health Organization (in press).
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Progress 01/01/02 to 12/31/02
Outputs
In the past year Dr. Munger made two visits to the Philippines to hold organizational meetings with colleagues from five field sites (Specific objective 1). The Philippines National Institutes of Health based at the University of the Philippines-Manila has been designated as the local coordinating center, under the leadership of Dr. Carmencita Padilla. Specific Objective 2 includes development of the data acquisition systems with geographical information systems (GIS) capabilities in collaboration with the USU Remote Sensing-GIS Center. In the past year detailed paper maps of the entire metropolitan Manila area have been obtained and are now at USU. The hiring of a graduate research assistant to support the mapping work was delayed because funding for this position was not approved in the original AES proposal. Funding has recently been provided for this position by the USU Center for Epidemiologic Studies and Mr. Samson Gebreab has been hired as a graduate research
assistant under the direction of Dr. Robert Gillies. Mr. Gebreab will work on making the digital maps of the metropolitan Manila area in the next year of the project. Specific Objective 3 includes linking and expanding oral cleft registries in five geographic areas of the Philippines. In the past year efforts have been focused on the largest and most challenging geographic area--metropolitan Manila. Under the leadership of Dr. Padilla, two national medical organizations in the Philippines representing plastic surgeons and ENT (ear, nose, and throat) surgeons have agreed to participate in a oral cleft patient registry; their members represent 20 major hospitals in Manila where oral cleft reconstructive surgeries are conducted and these will be major sources of case reports. In addition, two important non-governmental organizations that provide free cleft repair surgery for indigent patients, the Philippine Band of Mercy and Operation Smile-Philippines, have each agreed to participate.
Dr. Munger will coordinate the participation of USU in a memorandum of agreement with the Philippines NIH and these organizations. Drs. Padilla and Munger reviewed and revised data collection forms for the Manila oral cleft registry. We have decided to first organize the Manila oral cleft registry before attempting this in the other four sites. Data previously collected from the Philippines on biochemical markers of folate and vitamin B-6 status of mothers of oral cleft children and unaffected controls have been analyzed by Dr. Munger and Dr. Chris Corcoran (USU Department of Mathematics and Statistics). A statistical interaction between case-control status and levels of folate and vitamin B-6 status was observed in which the association between folate level and risk of oral clefts was dependent on the background level of vitamin B-6 status; vitamin B-6 status was associated with cleft risk independent of folate status. These findings have important implications for the design of an
intervention trial in which both vitamins are administered. Further investigation of vitamin B-6 status is underway, with additional samples recently collected in Cebu, central Philippines.
Impacts
The establishment of an oral cleft patient registry in metropolitan Manila is underway and is critical for the development of oral cleft prevention studies. This patient registry will also be a valuable resource for health planners and researchers from many fields in the Philippines and a model for registry development in other geographic areas of the Philippines.
Publications
- Mitchell, L. E., Beaty, T. H., Lidral, A. C., Munger, R. G., Murray, J. C., Saal, H. M., Wyszynski, D. F. Guidelines for the design and analysis of studies on nonsyndromic cleft lip and cleft palate in humans: summary report from a workshop of the international consortium for oral clefts genetics. Cleft Palate Craniofac J. 2002;39(1):93-100.
- Munger, R.G. (2002). Maternal nutrition and oral clefts. In: Cleft Lip and Palate: from Origin to Treatment. D. Wyzsynski., Editor. Oxford University Press, New York.
- Munger, R.G. (2002) The prevention of craniofacial anomalies. In: Global Strategies to Reduce the Health-Care Burden of Craniofacial Anomalies. Report of WHO meetings on International Collaborative Research on Craniofacial Anomalies. World Health Organization. Geneva.
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