Overview of Right From the Start Research

 

Right From the Start’s Legacy

 

RFTS grew from three “parent” studies which created and sustained this large community-recruited cohort. The three primary grants pivoted on research questions about:

Water Disinfection By-Products & Pregnancy Health

Uterine Fibroids & Pregnancy Health

Pain Medication Use & Pregnancy Health

 

 

Supplemental Studies, are those with additional funding to address focused questions alongside aspects of RFTS. These included The Healthy Men Study, [and names of EPA/CDC water projects here]. Ancillary Studies, draw in part or in whole on robust data available from RFTS. Many of these nurtured the doctoral or master’s work of graduate students and post-doctoral trainees.

 

RFTS began in 1999 at the University of North Carolina School of Public Health, with Dr. David A. Savitz, the chair of epidemiology, as the principal investigator. The first phase was funded by the American Water Works Association Research Foundation. Two subsequent major phases were funded by National Institutes for Health as R01 grants to Dr. Katherine E. Hartmann. The study, data, and tracking of participants and children after pregnancy has been based at Vanderbilt University Medical Center since 2007.

 

While the participants ultimately made our work possible, a core team of 11 researchers brought the main phases of the study into being, implementing infrastructure, recruitment, and follow-up of those enrolled, and more than 20 others contributed specialized expertise in areas like men’s reproduction, chemical and environmental measures, and advanced statistical methods.

Scientific Publications Grouped by Study Phase

 

Publications here are listed alphabetically by the first author in the citation. Study results, as well as descriptions of study processes, measurement and data analysis or statistical methods, are grouped with the phase in which the approach was developed or applied. Commentary and new areas of research or demonstration of  methods that grew out of experiences, data, or samples from RFTS are also grouped within the related parent phase. An asterisk indicates the author was a student or trainee at the time of the work. Publications that relied on data across phases are listed with the phase that motivated the aims of the paper or with the final phase from which data was included.

 

PRIMARY PHASES

 

Water Disinfection By-Products, Halogenated Compounds, & Pregnancy Health (Phase I)

 

  1. Ashley DL, Blount BC, Singer PC, et al. Changes in blood trihalomethane concentrations resulting from differences in water quality and water use activities. Arch Environ Occup Health. 2005;60(1):7-15. PMID: 16961003.
  2. Backer LC, Lan Q, Blount BC, et al. Exogenous and endogenous determinants of blood trihalomethane levels after showering. Environ Health Perspect. 2008;116(1):57-63. PMID: 18197300. PMCID: PMC2199304.
  3. Forssén UM, Herring AH, Savitz DA, et al. Predictors of use and consumption of public drinking water among pregnant women. J Expo Sci Environ Epidemiol. 2007;17(2):159-169. PMID: 16670711.
  4. Gordon SM, Brinkman MC, Ashley DL, et al. Changes in breath trihalomethane levels resulting from household water-use activities. Environ Health Perspect. 2006;114(4):514-21. PMID: 16581538. PMCID: 1440773.
  5. Hinckley AF, Bachand AM, Nuckols JR, Reif JS. Identifying public water facilities with low spatial variability of disinfection by-products for epidemiological investigations. Occup Environ Med. 2005;62(7):494-499. PMID: 15961627. PMCID: PMC1741051. [Methods]
  6. Hoffman CS*, Mendola P, Savitz DA, et al. Drinking water disinfection by-product exposure and duration of gestation. Epidemiology. 2008;19(5):738-746. PMID: 18633329.
  7. Hoffman CS*, Mendola P, Savitz DA, Herring AH, Loomis D, Hartmann KE, Singer PC, Weinberg HS, Olshan AF. Drinking water disinfection by-product exposure and fetal growth. Epidemiology, 2008 Sept;19:729-37. PMID: 18633330.
  8. Hoffman CS*, Messer LC, Mendola P, Savitz DA, Herring AH, Hartmann KE. Comparison of gestational age at birth based on last menstrual period and ultrasound during the first trimester. Paediatr Perinat Epidemiol, 2008 Nov;22:587-96. PMID: 19000297.
  9. Horton BJ, Luben TJ, Herring AH, Savitz DA, Singer PC, Weinberg HS, Hartmann KE. The effect of water disinfection by-products on pregnancy outcomes in two southeastern US communities. J Occup Environ Med, 2011 Oct;53(10):1172-8. PMID: 21915074. PMCID: 3693937
  10. Lamvu G*, Lorenz C, Jonsson Funk M, Makarushka C, Hartmann K, Savitz D. Racial differences among reasons for participating in research of pregnancy outcomes: the Right From the Start experience. Gender Medicine, 2005 Sep;2(3):166-73. PMID: 16290889.
  11. Luben TJ, Olshan AF, Herring AH, Jeffay S, Strader L, Buus RM, Chan RL, Savitz DA, Singer PC, Weinberg HS, Perreault SD. The Healthy Men Study: an evaluation of exposure to disinfection by-products in tap water and sperm quality.  Environ Health Perspectives, 115:1169-76, 2007. PMID: 17687443. PMCID: PMC1940094. [Healthy Men’s Study]
  12. MacLehose RF*, Savitz DA, Herring AH, Hartmann KE, Singer PC, Weinberg HS. Drinking water disinfection by-products and time to pregnancy. Epidemiology, 2008 May;19(3):451-8. PMID: 18379423.
  13. Miltner RJ, Speth TF, Richardson SD, Krasner SW, Weinberg HS, Simmons JE. Integrated disinfection by-products mixtures research: disinfection of drinking waters by chlorination and ozonation/postchlorination treatment scenarios. J Toxicol Environ Health A. 2008;71(17):1133-48. PMID: 18636388. [Study Design Method]
  14. Nuckols JR, Ashley DL, Lyu C, Gordon SM, Hinckley AF, Singer P. Influence of tap water quality and household water use activities on indoor air and internal dose levels of trihalomethanes. Environ Health Perspect. 2005;113:863–870. PMID: 16002374.PMCID: PMC1257647.
  15. Olshan AF, Luben TJ, Hanley NM, et al. Preliminary examination of polymorphisms of GSTM1, GSTT1, and GSTZ1 in relation to semen quality. Mutat Res. 2010;688(1-2):41-46. PMID: 20214911. PMCID: PMC3321349. [Healthy Men’s Study]
  16. Promislow HE*, Makarushka CM, Gorman JR, Howards PP*, Savitz DA, Hartmann KE. Recruitment for a community-based study of early pregnancy: The Right from the Start Study. Paediatr Perinat Epidemiol, 2004 Mar;18(2):143-52. PMID: 14996255.
  17. Richardson SD, Thruston AD Jr, Krasner SW, et al. Integrated disinfection by-products mixtures research: comprehensive characterization of water concentrates prepared from chlorinated and ozonated/postchlorinated drinking water. J Toxicol Environ Health A. 2008;71(17):1165-1186. PMID: 18636390. [Method/Measurement]
  18. Rossman LA, Brown RA, Singer PC, Nuckols JR. DBP formation kinetics in a simulated distribution system. Water Res. 2001;35(14):3483-89. PMID: 11547872. [Method]
  19. Saville BR, Herring AH. Testing random effects in the linear mixed model using approximate Bayes factors. Biometrics. 2009;65(2):369-76. PMID: 18759835. PMCID: PMC3136354. [Statistical Methods]
  20. Savitz DA, Chan RL, Herring AH, Howards PP, Hartmann KE. Caffeine and miscarriage risk. Epidemiology, 2008 Jan;19(1):55-62. PMID: 18091004.
  21. Savitz DA, Singer PC, Herring AC, Hartmann KE, Weinberg HS, Makarushka C. Exposure to drinking water disinfection by-product exposure and pregnancy loss. Am J Epidemiol, 2006 Dec;164(11):1043-51. PMID: 16957027
  22. Savitz DA. Invited commentary: biomarkers of exposure to drinking water disinfection by-products–are we ready yet? Am J Epidemiol. 2012;175(4):276-78. PMID: 22156021. [Related Review/Commentary]
  23. Silva LK, Backer LC, Ashley DL, et al. The influence of physicochemical properties on the internal dose of trihalomethanes in humans following a controlled showering exposure. J Expo Sci Environ Epidemiol. 2013;23(1):39-45. PMID: 22829048. [Methods]
  24. Singer PC. Variability and assessment of disinfection by-product concentrations in water distribution systems. In: Craun GF, Hauchman FS, Robinson DE, eds. Microbial Pathogens and Disinfection By-Products in Drinking Water: Health Effects and Management of Risks. Washington, DC: International Life Science Institute; 2001:211-223.
  25. Symanski E, Savitz DA, Singer PC. Assessing spatial fluctuations, temporal variability, and measurement error in estimated levels of disinfection by-products in tap water: implications for exposure assessment. Occup Environ Med. 2004;61(1):65-72. PMID: 14691275. PMCID: PMC1757819
  26. Weinberg HS, Pereira VR, Singer PC, Savitz DA. Considerations for improving the accuracy of exposure to disinfection by-products by ingestion in epidemiologic studies. Sci Total Environ. 2006;354(1):35-42. PMID: 16376695.
  27. Weinberg HS. Modern approaches to the analysis of disinfection by-products in drinking water. Philos Trans A Math Phys Eng Sci. 2009;367(1904):4097-4118. PMID: 19736235. [Measurement Methods]
  28. Wright JM, Murphy PA, Nieuwenhuijsen MJ, Savitz DA. The impact of water consumption, point-of-use filtration and exposure categorization on exposure misclassification of ingested drinking water contaminants. Sci Total Environ. 2006;366(1):65-73. PMID: 16126253.
  29. Yang J*, Hartmann KE, Herring AH, Savitz DA. Reducing misclassification in assignment of timing of events during pregnancy. Epidemiology, 2005 Jan;16(1):121-3. PMID: 15613955 [Methods]

 

Uterine Fibroids & Pregnancy Health (Phase II)

 

  1. Bray MJ*, Edwards TL, Wellons MF, Jones SH, Hartmann KE, Velez Edwards DR. Admixture mapping of uterine fibroid size and number in African American women. Fertil Steril 2017;108:1034-42.e26. PMID: 29202956. PMCID: PMC5728674.
  2. Buckley JP*, Palmieri RT*, Matuszewski JM, Herring AH, Baird DD, Hartmann KE, Hoppin JA. Consumer product exposures associated with urinary phthalate levels in pregnant women. J Expo Sci Environ Epidemiol, 2012 Sep;22(5):468-75. PMID: 22760436. PMCID: PMC3439834.
  3. Cate FL, Moffett C, Gronowski AM, Grenache DG, Hartmann KE, Woodworth A. Analytical and clinical validation of the Immulite 1000 hCG assay for quantitative analysis in urine. Clin Chim Acta, 2013 Jun 5;421:104-8. PMID: 23470427. PMCID: PMC3856699.  [Related Methods]
  4. Chan RL, Olshan AF, Savitz DA, et al. Severity and duration of nausea and vomiting symptoms in pregnancy and spontaneous abortion. Hum Reprod. 2010;25(11):2907-2912. PMID: 20861299. PMCID: PMC3140259.
  5. Edwards TL, Michels KA, Hartmann KE, Velez Edwards DR. BET1L and TNRC6B associate with uterine fibroid risk among European Americans. Hum Genet 2013;132:943-53. PMID: 23604678. PMCID: PMC3715562.
  6. Edwards TL, Hartmann KE, Velez Edwards DR. Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans. Hum Genet 2013;132:1361-9. PMID: 23892540.PMCID: PMC3830582.
  7. Hartmann KE, Velez Edwards DR, Savitz DA, Jonsson-Funk ML, Wu P, Sundermann AC*, Baird DD. Prospective cohort study of uterine fibroids and miscarriage risk. Am J Epidemiol. 2017 Nov;186(10):1140-48. PMID: 28591761. PMCID: PMC5860279.  [Authors reply: Am J Epidemiol 2018;187:1133-4.]
  8. Hasan R*, Baird DD, Herring AH, Olshan AF, Jonsson Funk ML, Hartmann KE. Association between first-trimester vaginal bleeding and miscarriage. Obstet Gynecol, 2009 Oct;114(4):860-7. PMID: 19888046. PMCID: PMC2828396.
  9. Hasan R*, Baird DD, Herring AH, Olshan AF, Jonsson Funk ML, Hartmann KE. Patterns and predictors of vaginal bleeding in the first trimester of pregnancy. Ann Epidemiol 2010;20:524-31. PMID: 20538195. PMCID: PMC2884141.
  10. Hasan R*, Funk ML, Herring AH, Olshan AF, Hartmann KE, Baird DD. Accuracy of reporting bleeding during pregnancy. Paediatr Perinat Epidemiol 2010;24:31-4. PMID: 20078827. PMCID: PMC2828393.
  11. Hasan R*, Olshan AF, Herring AH, Savitz DA, Siega-Riz AM, Hartmann KE. Self-reported vitamin supplementation in early pregnancy and risk of miscarriage. Am J Epidemiol 2009;169:1312-8. PMID: 19372214. PMCID: PMC2727248.
  12. Johnson G*, MacLehose RF, Baird DD, Laughlin ST, Hartmann KE. Uterine leiomyomata and fecundability in the Right from the Start study. Human Reprod, 2012 Oct;27(10):2991-7. PMID: 22811308. PMCID: 3442631.
  13. Laughlin SK*, Baird DD, Savitz DA, Herring AH, Hartmann KE. Prevalence of uterine leiomyomas in the first trimester of pregnancy: An ultrasound-screening study. Obstet Gynecol, 2009 Mar;113(3):630-5. PMID: 19300327. PMCID: 3384531.
  14. Laughlin SK*, Herring AH, Savitz DA, Olshan AF, Fielding JR, Hartmann KE, Baird DD. Pregnancy-related fibroid reduction. Fertil Steril, 2010 Nov;94(6):2421-3. PMID: 20451187. PMCID: 2927730.
  15. Laughlin SK, Hartmann KE, Baird DD. Postpartum factors and natural fibroid regression. Am J Obstet Gynecol, 2011 Jun;204(6):496.e1-6. PMID: 21492823. PMCID: 3136622.
  16. Michels K*, Hartmann KE, Archer KR, Ye F, Velez Edwards DR. Relationship between total fibroid burden and first trimester bleeding and pain. Paediatric Perinat Epidemiol, 2016 Mar;30(2):115-23. PMID: 26525634. PMCID: 4749406.
  17. Michels KA*, Velez Edwards DR, Baird DD, Savitz DA, Hartmann KE. Uterine leiomyomata and cesarean birth risk: a prospective cohort with standardized imaging. Ann Epidemiol 2014;24:122-6. PMID: 24321612. PMCID: PMC3926444.
  18. Myers SL, Baird DD, Olshan AF, Herring AH, Schroeder JC, Nylander-French LA, Hartmann KE. Self-report versus ultrasound measurement of uterine fibroid status. J Womens Health (Larchmt), 2012 Mar; 21(3):285-93. PMID: 22044079. PMCID: 3298676.
  19. Slaughter JC*, Herring AH, Hartmann KE. Bayesian modeling of embryonic growth using latent variables. Biostatistics, 2008 Apr;9(2):373-89. PMID: 18056115. [Statistical Methods]
  20. Sundermann AC, Velez Edwards DR, Bray MJ, Jones SH, Latham SM, Hartmann KE. Leiomyomas in pregnancy and spontaneous abortion: a systematic review and meta-analysis. Obstet Gynecol 2017;130(5):1065-72. PMID: 29016496. PMCID: 5656535. [Related Review]
  21. Velez Edwards DR, Baird DD, Hartmann KE. Association of age at menarche with increasing number of fibroids in a cohort of women who underwent standardized ultrasound assessment. Am J Epidemiol 2013;178:426-33. PMID: 23817917. PMCID: PMC3727338.
  22. Wang L, Dunson DB. Semiparametric Bayes’ proportional odds models for current status data with underreporting. Biometrics. 2011;67(3):1111-18. PMID: 21175554. PMCID: PMC3616323. [Statistical Methods]
  23. Zhao SK*, Wu P, Jones SH, Torstenson SK, Hartmann KE, Velez Edwards DR. Association of uterine fibroids with birthweight and gestational age. Ann Epidemiol. 2020, July. https://doi.org/10.1016/j.annepidem.2020.06.012 
  24. Sundermann AC*, Aldridge, TD*, Hartmann KE, Jones SH, Torstenson ES, Velez Edwards DR. Uterine fibroids and risk of preterm birth by clinical subtypes. BMC Pregnancy Childbirth. 2021;21(1):560. PMID: 34404377

 

Fibroid Research Facilitated by RFTS Samples, Ultrasounds, Fibroid Classification, or Data Methods

 

  1. Edwards TL, Michels KA, Hartmann KE, Velez Edwards DR. BET1L and TNRC6B associate with uterine fibroid risk among European Americans. Hum Genet 2013;132:943-53. PMID: 23604678. PMCID: PMC3715562.
  2. Edwards TL, Hartmann KE, Velez Edwards DR. Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans. Hum Genet 2013;132:1361-9. PMID: 23892540. PMCID: PMC3830582.
  3. Feingold-Link L*, Edwards TL, Jones S, Hartmann KE, Velez Edwards DR. Enhancing uterine fibroid research through utilization of biorepositories linked to electronic medical record data. J Women’s Health (Larchmt), 2014 Dec;23(12):1027-32. PMID: 25495367. PMCID: 4267124.
  4. Velez Edwards DR*, Hartmann KE, Wellons M, Shah A, Xu H, Edwards TL. Evaluating the role of race and medication in protection of uterine fibroids by type 2 diabetes exposure. BMC Womens Health, 2017 Apr 11;17(1):28. PMID: 28399866. PMCID: 5387248
  5. Giri A*, Edwards TL, Hartmann KE, Torstenson ES, Wellons M, Schreiner PJ, Velez Edwards DR. African genetic ancestry interacts with body mass index to modify risk for uterine fibroids. PLoS Genet. 2017 Jul;13(7):e1006871. PMID: 28715450. PMCID: 5536439
  6. Hellwege JN*, Jeff JM, Wise LA, Gallagher CS, Wellons M, Hartmann KE, Jones SF, Torstenson ES, Dickinson S, Ruiz-Narváez EA, Rohland N, Allen A, Reich D, Tandon A, Pasaniuc B, Mancuso N, Im HK, Hinds DA, Palmer JR, Rosenberg L, Denny JC, Roden DM, Stewart EA, Morton CC, Kenny EE, Edwards TL, Velez Edwards DR. A multi-stage genome-wide association study of uterine fibroids in African Americans. Hum Genet. 2017 Oct;136(10):1363–73. PMID: 28836065. PMCID: 5628188.
  7. Bray MJ*, Edwards TL, Wellons MF, Jones SH, Hartmann KE, Velez Edwards DR. Admixture mapping of uterine fibroid size and number in African American women. Fertil Steril. 2017 Dec;108(6):1034–1042. PMID: 29202956. PMCID: PMC5728674.
  8. Edwards TL, Giri A*, Hellwege JN*, Hartmann KE, Stewart EA, Jeff JM, Bray MJ*, Pendergrass SA, Torstenson ES, Keaton JM, Jones SH, Gogoi RP, Kuivaniemi H, Jackson KL, Kho AN, Kullo IJ, McCarty CA, Im HK, Pacheco JA, Pathak J, Williams MS, Tromp G, Kenny EE, Peissig PL, Denny JC, Roden DM, Velez Edwards DR. A trans-ethnic genome-wide association study of uterine fibroids. Front Genet. 2019 Jun; 12;10:511. [Epub ahead of print] PMID: 31249589. PMCID: PMC6582231

 

Medication Use & Pregnancy Health (Phase III)

 

  1. Aldridge TD*, Hartmann KE, Michels KA*, Velez Edwards DR. First-trimester antihistamine exposure and risk of spontaneous abortion or preterm birth. Pharmacoepidemiol Drug Saf, 2014 Oct;23(10):1043-50. PMID: 24789281. PMCID: 4776748
  2. Mukherjee S*, Velez Edwards DR, Baird DD, Savitz D, Hartmann KE. Risk of miscarriage among black women and white women in a US prospective cohort study. Am J Ep idemiol, 2013 Jun 1;177(11):1271-8. PMID: 23558353. PMCID: 3664339.
  3. Pryor J*, Patrick SW, Sundermann AC*, Wu P, Hartmann, KE. Pregnancy intention and maternal alcohol consumption. Obstet Gynecol, 2017 Apr;129(4):727-33. PMID: 28277356. PMCID: 5679257.
  4. Sundermann AC*, Hartmann KE, Jones SH, Torstenson ES, Velez Edwards DR. Validation of maternal recall of early pregnancy medication exposure using prospective diary data. Ann Epidemiol, 2017 Feb;27(2):135-39. PMID: 28012836. PMCID: 5685497.
  5. Sundermann AC*, Hartmann KE, Jones SH, Torstenson ES, Velez Edwards DR. Interpregnancy interval after pregnancy loss and risk of repeat miscarriage. Obstet Gynecol. 2017 Dec;130(6):1312–18. PMID: 29112656. PMCID: 5709156.
  6. Sundermann AC*, Mukherjee S*, Wu P, Velez Edwards D, Hartmann KE. Gestational age at arrest of development: an alternative approach for assigning time at risk in studies of time-varying exposures and miscarriage. Am J Epid. 2019 Mar;188(3):570-78. PMID: 30521025. PMCID: 6395168.
  7. Sundermann AC*, Zhao S*, Young CL, Lam L, Jones SH, Velez Edwards DR, Hartmann KE. Alcohol use in pregnancy and miscarriage: a systematic review and meta-analysis. Alcohol Clin Exp Res. 2019 Aug; 43(8):1606-16. PMID: 31194258. PMCID: 6677630. [Related Review]
  8. Sundermann AC*, Velez Edwards DR, Slaughter JC , Wu, P, Jones, SP, Torstenson, ES, Hartmann KE. Week-by-week alcohol consumption in early pregnancy and miscarriage risk: A prospective cohort study. Am J Obstet Gynecol. 2021 Jan; 224(1): 97.e1-97.e16. PMID: 32673615.
  9. Velez Edwards DR*, Aldridge T*, Baird DD, Funk MJ, Savitz DA, Hartmann KE. Periconceptional over-the-counter nonsteroidal anti-inflammatory drug exposure and risk for spontaneous abortion. Obstet Gynecol, 2012 Jul;120(1):113-22. PMID: 22914399. PMCID: PMC3427532.
  10. Velez Edwards DR, Baird DD, Hasan R*, Savitz DA, Hartmann KE. First-trimester bleeding characteristics associate with increased risk of preterm birth: Data from a prospective pregnancy cohort. Hum Reprod, 2012 Jan;27(1):54-60. PMID: 22052384. PMCID: 3241603.
  11. Velez Edwards DR, Edwards TL, Bray MJ*, et al. Nonsteroidal anti-inflammatory drug interaction with prostacyclin synthase protects from miscarriage. Sci Rep 2017;7:9874.  PMID: 28852049. PMCID: PMC5575303.
  12. Velez Edwards DR, Hartmann KE. Racial differences in risk of spontaneous abortions associated with periconceptional over-the-counter nonsteroidal anti-inflammatory drug exposure. Ann Epidemiol, 2014 Feb;24(2):111-5. PMID: 24331921. PMCID: 3946756
  13. Wu P, Velez Edwards DR*, Gorrindo P*, Sundermann AC*, Torstenson ES, Jones SH, Chan RL, Hartmann KE. Association between first trimester antidepressant use and risk of spontaneous abortion. Pharmacotherapy. 2019 Sep;39(9):889-98 PMID: 31278762. PMCID: 6736709.