Reproductive Epidemiology Research
What is Reproductive, Perinatal, and Pediatric Epidemiology (RPPE)?
The health concerns faced in the field of reproductive, perinatal, and pediatric health are among the most pressing issues of our time, both from scientific and public perspectives. The ability to successfully reproduce and have a healthy child transcends other health concerns by touching on very basic human needs and desires. Whether the challenge is to understand and remedy causes of infertility, prevent prematurity or birth defects, or identify the causes of such highly visible, troubling disorders as autism or attention deficit disorder, epidemiologists have a central role that is just now being fully appreciated.
The University of North Carolina at Chapel Hill is a leader in the field of reproductive, perinatal and pediatric epidemiology. The academic departments of Epidemiology, Maternal and Child Health, Nutrition, Pediatrics, and Obstetrics and Gynecology have engaged in a variety of collaborative and individual projects to address substantive and methodological issues facing our field.
Faculty and students in the RPPE program are involved in a variety of ongoing research activities. Examples of research opportunities and projects within the RPPE program are listed below. Please click the links below for further information.
The Pregnancy, Infection, and Nutrition Study (PIN) (Dole N, Evenson K, Herring A, Olshan A, Siega-Riz AM, Thorp J – NIH, 8/95-12/05). This team of investigators has collaborated on the decade-long PIN study to investigate the epidemiology of preterm birth, one of the major contributors to perinatal morbidity and mortality in the United States. This study’s primary goal is to identify etiologic factors for preterm delivery, including preterm premature rupture of the membranes (PROM), delivery due to early onset of labor, and related complications of pregnancy, so that public health measures can be taken to reduce this adverse pregnancy outcome and its associated health, social, and economic costs. The PIN study has successfully recruited over 5000 pregnant women from central North Carolina to address physical activity, psychosocial factors, placental characteristics, postpartum weight retention, nutritional factors and food security, bacterial vaginosis and other genital tract infections, occupational physical exertion, smoking, sexual behavior during pregnancy, vaginal bleeding, genetic factors, as well as variety of health and social behaviors and community level factors.
The PIN Postpartum Study (Siega-Riz AM, Evenson K, Herring A, Dole N, Moos M-K, Thorp J, NIH, 8/02-7/07) was added as a major extension of the PIN study in 2002. This study follows women (n=689) for the first year post-partum to identify modifiable factors related to postpartum weight retention and postpartum mental health. The study collects data in the home 3 and 12 months after delivery including: maternal height, weight, and percent body fat using bioelectrical impedance, and an interview about diet, breastfeeding status, body image, behaviors, health and work status, physical activity, and psychosocial factors.. Focus groups during pregnancy and in-depth interviews during the postpartum period were conducted among a subset of women to collect qualitative information on barriers and enhancements to physical activity, healthy eating, and weight loss during the postpartum period. Dr. Siega-Riz collaborates with Dr. Evenson, who received funding to add a detailed assessment of physical activity and neighborhood factors to this, and Dr. Daniels, who has been following the growth and neurodevelopment of the infants.
North Carolina Center for Birth Defects Research and Prevention (Olshan A, Siega-Riz A, Herring A, Meyer R, CDC, 9/02-8/13). The North Carolina Center for Birth Defects Research and Prevention conducts surveillance and collaborates with Centers across the country to conduct case-control studies of risk factors for birth defects (the National Birth Defects Prevention Study). The national study now includes over 14,000 cases of birth defects and 8,000 controls. The Center is a close collaboration with the North Carolina Department of Public Health. Telephone interviews are conducted and DNA is collected by buccal cells to allow detailed evaluation of environmental, nutritional, and genetic factors that might be associated with specific birth defects. Dr. Olshan is currently evaluating trends in neural tube defects and other folic acid preventable birth defects following folic acid interventions, as well as inflammation, metabolizing enzyme, and DNA repair gene polymorphisms that may be associated with oral clefts, neural tube, and heart defects. Dr. Siega-Riz, a Center investigator, has begun evaluating nutritional factors associated with various birth defects such as gastroschisis, NTD’s, etc. Dr. Daniels mentored Cynthia Cassell, an MCH doctoral student with a minor in Epidemiology, who linked North Carolina Center for Birth Defects Research and Prevention data to state Medicaid data to conduct her dissertation research on the cost and services used by children with oral facial clefts.
Consequences and Course of Uterine Fibroids in Pregnancy (Olshan A, Baird D, Herring A, M. Funk, NIH, 1/04-12/08-PI now at Vanderbilt-Kathy Hartmann). This study evaluates the association of fibroids with specific adverse pregnancy outcomes, such as early pregnancy loss and preterm birth, while investigating the natural history of fibroids during and after pregnancy in an ethnically diverse population. The study is recruiting a cohort of 3,300 ethnically diverse women from 13 counties in North Carolina. This study will contribute to our understanding of the reproductive effects of fibroids (spontaneous abortion, preterm birth, etc.) and fibroid growth patterns during pregnancy as they relate to maternal age, race, BMI, maternal weight gain, clinical glucose tolerance measures, hypertension, pregnancy outcome, lactation, or post-pregnancy contraceptive choice. Several doctoral students have been engaged in research through this project, Rachel Palmieri (Epidemiology) focusing on reliability of fibroid identification and classification, Reem Hasan (Epidemiology) implementing a web-based daily diary system to collect medication exposure and symptom data, and Ronna Chan (MCH), related to nausea and spontaneous abortion.
Physical and Sexual Violence Among North Carolina Residents (Martin S., NC Dept of Health and Human Services, 11/03-10/04). This study focuses on violence against women, including violence during pregnancy and the postpartum period. Dr. Martin mentored Cecila Casanueva an MCH doctoral student who completed her dissertation on this topic. Another student, Ronna Chan, who is minoring in Epidemiology, during her research practicum examined whether women’s and men’s experiences of sexual and physical violence were associated with their use of contraception and family planning services. Findings from this research were presented at a scientific meeting and a manuscript is in the peer review process.
Randomized Trial of Iron Supplementation during Pregnancy (Siega-Riz A, ASPH/CDC, 1/97-12/2002). This study evaluated iron status in the third trimester following the randomization of study participants into 4 iron supplementation groups based on initial serum ferritin values in relation to birth outcomes. A total of 867 women from the prenatal clinic at the Wake County Human Services in Raleigh, North Carolina participated in the study. Dr. Siega-Riz mentored two dissertations from these data, Lisa Bodnar and Sunitha Jasti which lead to 8 published papers.
Malaria and HIV in Pregnant Women in Malawi (Meshnick S, NIH, 3/01-2/06). Approximately 500,000 HIV-infected children are born each year in sub-Saharan Africa. Nevirapine treatment programs could prevent about half of these infections. In Africa, maternal malaria is common and frequently causes low birth weight. Important interactions between HIV and malaria infections in pregnant women have been identified and low-cost interventions to prevent maternal malaria are known. This study has enrolled 1400 women at antenatal clinics in Blantyre, Malawi to evaluate whether maternal malaria increases mother-to-child HIV transmission in nevirapine-treated women and children. Dr. Meshnick mentored two doctoral students who completed their dissertation research using data from this study: Sarah Landis evaluated the effects of malaria on intrauterine fetal growth, as well as whether uterine or umbilical blood flow abnormalities are associated with either malaria and/or poor birth outcomes. Linda Kalilani evaluated the effects of malaria on pregnancy in Malawi and conducting a small clinical trial comparing three antimalarial treatment regimens in pregnant women.
A Pilot Study of Immunologic and Virologic Correlates of Mother to Child HIV-1 Transmission via Breast Milk (Meshnick NIH NIAID CHAVI-009, 1/1/07-12/31/08). This is a prospective cohort study of 250 HIV-infected mothers and their babies to identify risk factors for HIV transmission. Whole genome analyses will be done on all mothers and infants. The data will be analyzed by a current Epidemiology PhD student, Bonnie Pedersen.
Vanguard Center for the National Children’s Study in Duplin County, North Carolina (NICHD Contract # HHSN275200503413C, Barbara Entwisle, PI; Nancy Dole, Co-PI; Anna Maria Siega-Riz, Andy Olshan, Amy Herring, and John Thorp, Co-investigators). The Carolina Population Center at UNC is collaborating with Duke University, Battelle Memorial Institute, and Mount Sinai School of Medicine to conduct the study in Duplin County. The National Children’s Study will examine the effects of environmental influences on the health and development of children in the United States. The study will identify a national probability sample of 100,000 children, before pregnancy or as early as possible in pregnancy, and follow them for 21 years to address the causes of a variety of health problems including obesity, injuries, asthma, and developmental delays. Natural and man-made environmental factors, biological and chemical factors, physical surroundings, social, behavioral, cultural, and family factors, genetics, and geographic location are all included. Fieldwork is scheduled to begin this summer. The team has also submitted a bid for the other 6 NCS sites in North Carolina.[back to top]
Neurodevelopment and HIV/AIDS (Van Rie A, NIH, 9/03-8/05). The HIV/AIDS epidemic has resulted in a parallel rise in the numbers of orphaned children and a rapidly expanding pediatric HIV/AIDS epidemic. The WHO estimates that 3.2 million children are living with HIV/AIDS in 2002 and 800,000 children were newly infected in the year 2002 alone. UNAIDS estimates that there will be 24 million AIDS orphans by the year 2010. The impact of HIV/AIDS on the health of African children remains poorly documented. Limited data on the health and nutritional status of HIV infected children and AIDS orphans are available. The neurodevelopment of HIV infected children and AIDS orphans growing up in families devastated by HIV/AIDS has, however, not been subject of rigorous research. Dr. Van Rie’s planning project is building a collaborative research infrastructure that will contribute to the long-term capacity to conduct neurodevelopment research at the University of Kinshasa. Her new grant, a prospective longitudinal community-based study, will start enrollment in fall 2007. The aims of the study are to determine the first order (HIV exposure and infection) and second order (maternal AIDS and AIDS orphans) effects of the HIV epidemic on the neurodevelopment of young children, perform a cross-sectional characterization of HIV env compartmentalization in the CNS in HIV-infected infants (prior to initiating ART, test the hypothesis that unique HIV env lineages are present in CNS versus peripheral compartments, and to provide insight into the pathogenesis of HIV-associated CNS disease in young children. It is expected that at least one and most likely two doctoral students will conduct their dissertation research using the data from this study. Anna Dow, a doctoral student mentored by Dr. Van Rie has worked on this project.
The North Carolina Center for Autism and Developmental Disabilities Epidemiology (Daniels J, CDC, 9/02-9/06, Surveillance Renewal funded 6/06-5/10). It is not currently known how many children North Carolina have autism, but there is great concern about potentially rising rates of autism. The Center studies autism and mental retardation in North Carolina in collaboration with other similar sites around the country. The Center conducts active surveillance for autism and mental retardation among children in central North Carolina and is planning a collaborative multi-site study of risk factors for autism. The Center is also collaborating with investigators at the Sheps Center to identify service and treatment patterns and costs. Dr. Daniels mentors Amy Kalkbrenner, a doctoral student in Epidemiology, who is planning to use this data do study whether the prevalence of autism varies by geographic varying environmental exposures, demographics, and access to health care factors.
Assessment of Perinatal PBDE Exposure and related Child Behavioral and Cognitive Developmental Effects (Daniels J, EPA, 3/06-3/09). The primary aim of the study is to investigate children s exposure to PBDEs through breast milk, diet and their physical environment in relation to cognitive and behavioral development. This study follows a subcohort of the children born to participants of the PIN studies until they are 3 years of age. Home visits are conducted at 3, 12 and 36 months to investigate a variety of environmental exposures that may affect their health, including PBDEs, diet, and social factors, and assess the child s general health, neurodevelopment, and anthropometry. Participants of this study are children born to participants of two existing studies: the Pregnancy, Infection, and Nutrition (PIN) Study follows women through the end of pregnancy, then the PIN Postpartum Study continues to follow them through the first year postpartum. Linkage with these studies provides considerable information on the mothers during pregnancy, including diet, stress, psychosocial health, infection, weight status, physical activity, and blood samples. This study will offer students many opportunities to evaluate exposures during pregnancy and early life in relation to children’s health. Recently, Sarah Keim and I-Jen Pan used this data set for their dissertation.
Infant Care, Feeding and Risk of Obesity (Bentley M, Siega-Riz A, Adair L, NIH, 4/02-3/07). This study examine household and community factors that influence parenting and infant feeding patterns, the relationship of feeding styles to infant dietary intake and the relationship of dietary intakes and activity patterns to infant fatness. The study is conducted among African American mothers and infants in North Carolina, a group at high risk for the development of obesity. A PhD graduate from the nutrition program serves as project manager and it has involved 3 nutrition doctoral students. The students attend biweekly project meetings, participated in decision making about issues such as sample recruitment, assisted in the development of survey instruments and conducted interviews with study respondents.
The Cebu Longitudinal Health and Nutrition Survey(CLHNS) *(Adair, L HL085144-01 (08/01/06-07/31/10) Obesity Development and CVD Risk Factor Clustering in Filipino Women & Offspring ; TW05596-05 (05/05/01-04/30/08) Effect of Health on Education & Work in Filipino Youth ; and DK 078150 (4/1/2007-3/31/2011) Genetic Epidemiology of Body Mass Index, Adiposity and Weight Gain) This is a longitudinal cohort of women followed from the last trimester of pregnancy and their offspring from birth to age 21. Women were recruited from randomly selected communities of Metro Cebu, Philippines. Detailed dietary, anthropometric, behavioral, and environmental variables were collected from mothers during pregnancy. Bi-monthly surveys from birth to 24 months provide data on child feeding and illnesses. Together, these data allow for the study of the long term effects of the prenatal and early postnatal environment on many aspects of child and young adult health and well being. Ongoing studies are examining the effects of early child nutrition on school attainment and productivity of young adults well as on physical growth and the development of cardiovascular disease risk factors. This study has led to many dissertations and student publications over the years.
Obesity and the Environment: The Transition to Adulthood (Gordon-Larsen P, NIH, (05/03-04/08). This research will generate and link geocoded locations of respondents and physical environment variables to data from two exceptional and unique longitudinal datasets, the National Longitudinal Study of Adolescent Health (Add Health) and the Coronary Artery Risk Development in Young Adults Study (CARDIA). The aim of this research is to investigate environmental effects on physical activity and obesity in the transition to adulthood. It is led by Penny Gordon-Larsen. This project is part of a larger research effort on two datasets, Add Health and CARDIA. The project has supported one nutrition doctoral student who completed her doctoral training using data generated from this project and is on faculty at the University of Minnesota.
Physical Environment Dynamics, Inequality and Obesity (Gordon-Larsen P, Popkin BM, Adair LS, Guilkey D, NIH 07/03-06/07). This study focuses on how numerous community characteristics interact with race/ethnicity and other key socioeconomic factors to affect physical activity, inactivity, and overweight status in American youths as they make the transition from adolescence to adulthood. A particular interest of this project is exploring the determinants of overweight for adolescents as they become young adults and begin to marry and have children. This study uses data from over 20,000 ethnically diverse adolescents enrolled in the National Longitudinal Study of Adolescent Health (Add Health) and is led by Penny Gordon-Larsen and Barry Popkin. This project has supported three nutrition doctoral students who have collectively written 11 papers.
Genetic Susceptibility Factors in the Etiology of Neuroblastoma (Olshan A, Siega-Riz AM, NIH 08/01/08 – 07/30/13). Over a five-year period, the Neuroblastoma Epidemiology in North America (NENA) study seeks to enroll approximately 600 children (living and deceased) who were diagnosed with neuroblastoma before 6 years of age. In addition, NENA is enrolling the biological mothers and biological fathers of these children. In this way, biological triads can be studied which allows NENA to explore the genetics of the disease. Children with neuroblastoma, along with their biological parents, are recruited from the US, Puerto Rico and Canada to participate in this research.[back to top]
In addition to the faculty research on campus, several affiliated faculty at near-by research institutions provide exciting research opportunities for our students as well.
The EPA epidemiologists are based on the UNC campus. Their proximity and expertise has increased the number of projects available for student research under the co-mentorship of EPA investigators. For example, Sharon Sagiv recently completed her dissertation research under the guidance of Drs. Pauline Mendola and Dana Loomis (who until recently was a member of the Department) She analyzed air pollution and preterm birth at four carefully selected locations in Pennsylvania and is working to publish the papers resulting from that effort. In 2005, Richard Kwok, mentored by Drs. Savitz and Mendola, completed his dissertation based on an EPA study of arsenic and blood pressure during pregnancy using data from a study he helped to conduct and manage. Both students have presented at international meetings and have published (or submitted) their work. Additional research opportunities in asthma epidemiology are available through Dr. Lucas Neas, who directs the El Paso Children’s Health Study and the Detroit Children’s Health Study. Amy Kalkbrenner, an Epidemiology doctoral student, contributed to the design of the data collection instruments for the Detroit study as a part of her field pre-doctoral training.
NIEHS is located less than 20 minutes from UNC in Research Triangle Park. Investigators at NIEHS mentor a number of UNC epidemiology students in ongoing research projects. Prior to conducting her dissertation research on the PIN study, Emily Harville worked with Dr. Allen Wilcox to write two papers describing facial clefts in Norway using data from the Norwegian Medical Birth Registry. Upcoming research opportunities include working with Dr. London’s study of Childhood Asthma Genetics in Mexico City and Dr. Longnecker’s investigation of in utero exposure to perfluorinated alkyls in relation to neonatal thyroid function and childhood growth, which is nested in the Norwegian Mother and Child Cohort Study. The Norwegian Mother and Child Cohort is a prospective study of 100,000 women enrolled during pregnancy, and their children are then followed to young adulthood. The Generation R cohort study will evaluate in utero exposure to phthalates and bisphenol A in relation to duration of gestation, childhood respiratory disease, and overweight. The Agricultural Health Study provides enrolled approximately 32,000 spouses of pesticide applicators between 1995 and 1997 and has tracked their children and provides an opportunity to evaluate the influence of pesticide exposure on ovarian function and child health. Under the direction of Drs. Glinda Cooper and David Savitz, doctoral student Sherry Farr used these data for her dissertation research on pesticide use, menstrual cycle characteristics, and age at natural menopause.
Annelies Van Rie
|Below is a listing of some of our current students associated with the RPPE program area:
The RPPE program area provides students with a multidisciplinary perspective, a strong foundation in epidemiologic concepts and methods, and an understanding of the underlying biology of reproduction and childhood development and growth. The program prepares students to pursue careers in reproductive, perinatal and pediatric epidemiologic research.
Through their participation in the program, students gain an understanding of the following:
As a part of the RPPE curriculum, students perform course work in the Departments of Epidemiology, Biostatistics, Maternal and Child Health, Nutrition and Biology; attend seminars and journal clubs regarding innovative and developing research topics; and conduct research under the guidance of experienced program faculty.
In addition to core requirements for completion of graduate degrees in the Department of Epidemiology, the RPPE program includes two required and several recommended courses which fit the diverse interests of students.
|RPPE Training Grant
The RPPE Training Grant offers 5 predoctoral positions that provide stipend, tuition remission, health insurance, and some travel costs. Interested students in the Departments of Maternal and Child Health, Nutrition, and Epidemiology are encouraged to apply. Application for Training Grant positions is competitive.
Graduate Student Research Assistantships
Research assistantships (RAs) offer students an opportunity to gain research-related experience, develop close working relationships with faculty, and sometimes earn CO-authorship on peer-reviewed publications. Information on the type of assistantships available and how to locate them is available from Student Services. A small number of RA positions are typically available in the RPPE program. Students interested in an assistantship should submit an application form (available from Student Services), and should discuss this interest with their advisors.
Some students in the RPPE program have secured funding through sources that are external to the Department or the University. Please click on the links below for further information about some of these external funding sources.