Pregnancy Health

Our lab has existing research projects focused on examining genetic risk factors for adverse pregnancy outcomes in a large epidemiologic pregnancy cohort. For these studies I am working with Right from the Start (RFTS). RFTS is an ongoing, community-based prospective cohort study with the goal of advancing knowledge about maternal and fetal health from conception to birth. Since 1999, RFTS has enrolled more than 6,000 women, 20% prior to conception, in order to study determinants of fecundability, miscarriage, spontaneous preterm birth, and other adverse pregnancy outcomes. Data have been carefully collected with regard to quality control and the data set has reached sufficient size to have good power to investigate additional important etiologic and clinically relevant questions. We have collected DNA samples from past and current RFTS participants and their children to ask new questions regarding the etiology of pregnancy and its adverse outcomes. Current studies include examining maternal nonsteroidal-anti-inflammatory drug (NSAID) exposure during preconception and early pregnancy on risk for spontaneous abortion as well as studies examining environmental exposures on risk for spontaneous preterm birth. We have also developed multiple studies evaluating the role genetic determinants of adverse pregnancy outcomes using the BioVU DNA biorepository. Below are our publications related to RFTS and studies using other resources to evaluate adverse pregnancy outcomes.

Relevant Publications

Right from The Start

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): 1312-8. PMID: 29112656, PMCID: PMC5709156, DOI: 10.1097/AOG.0000000000002318, ISSN: 1873-233X. 

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 [print-electronic]. 2017 Oct 10/6/2017; PMID: 29016496, DOI: 10.1097/AOG.0000000000002313, ISSN: 1873-233X. 

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 [print-electronic]. 2017 Jun 6/7/2017; 1-9. PMID: 28591761, PII: 3859593, DOI: 10.1093/aje/kwx062, ISSN: 1476-6256. 

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 [print-electronic]. 2017 Feb; 27(2): 135-139.e2. PMID: 28012836, PII: S1047-2797(16)30531-2, DOI: 10.1016/j.annepidem.2016.11.015, ISSN: 1873-2585. 

Burrows CK, Kosova G, Herman C, Patterson K, Hartmann KE, Velez Edwards DR, Stephenson MD, Lynch VJ, Ober C. Expression Quantitative Trait Locus Mapping Studies in Mid-secretory Phase Endometrial Cells Identifies HLA-F and TAP2 as Fecundability-Associated Genes. PLoS Genet. 2016 Jul; 12(7): e1005858. PMID: 27447835, PMCID: PMC4957750, PII: PGENETICS-D-15-02797, DOI: 10.1371/journal.pgen.1005858, ISSN: 1553-7404. 

Michels KA, Hartmann KE, Archer KR, Ye F, Velez Edwards DR. The Relationship between Total Fibroid Burden and First Trimester Bleeding and Pain. Paediatr Perinat Epidemiol [print-electronic]. 2015 Nov 11/3/2015; PMID: 26525634, DOI: 10.1111/ppe.12256, ISSN: 1365-3016. 

Aldridge TD, Hartmann KE, Michels KA, Velez Edwards DR. First-trimester antihistamine exposure and risk of spontaneous abortion or preterm birth. Pharmacoepidemiol Drug Saf [print-electronic]. 2014 Oct; 23(10): 1043-50. PMID: 24789281, DOI: 10.1002/pds.3637, ISSN: 1099-1557. 

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 [print-electronic]. 2014 Feb; 24(2): 111-115.e1. PMID: 24331921, PMCID: PMC3946756, PII: S1047-2797(13)00417-1, DOI: 10.1016/j.annepidem.2013.11.001, ISSN: 1873-2585. 

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 [print-electronic]. 2014 Feb; 24(2): 122-6. PMID: 24321612, PMCID: PMC3926444, PII: S1047-2797(13)00412-2, DOI: 10.1016/j.annepidem.2013.10.017, ISSN: 1873-2585.

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 [print-electronic]. 2013 Dec; 132(12): 1361-9. PMID: 23892540, PMCID: PMC3830582, DOI: 10.1007/s00439-013-1340-1, ISSN: 1432-1203. 

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 [print-electronic]. 2013 Aug 8/1/2013; 178(3): 426-33. PMID: 23817917, PMCID: PMC3727338, PII: kws585, DOI: 10.1093/aje/kws585, ISSN: 1476-6256.

Edwards TL, Michels KA, Hartmann KE, Velez Edwards DR. BET1L and TNRC6B associate with uterine fibroid risk among European Americans. Hum. Genet [print-electronic]. 2013 Aug; 132(8): 943-53. PMID: 23604678, PMCID: PMC3715562, DOI: 10.1007/s00439-013-1306-3, ISSN: 1432-1203. 

Mukherjee S, Velez Edwards DR, Baird DD, Savitz DA, Hartmann KE. Risk of miscarriage among black women and white women in a U.S. Prospective Cohort Study. Am. J. Epidemiol [print-electronic]. 2013 Jun 6/1/2013; 177(11): 1271-8. PMID: 23558353, PMCID: PMC3664339, PII: kws393, DOI: 10.1093/aje/kws393, ISSN: 1476-6256. 

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, PII: 00006250-201207000-00019, DOI: 10.1097/AOG.0b013e3182595671, ISSN: 1873-233X. 

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 [print-electronic]. 2012 Jan; 27(1): 54-60. PMID: 22052384, PMCID: PMC3241603, PII: der354, DOI: 10.1093/humrep/der354, ISSN: 1460-2350. 

Velez Edwards DR, Edwards TL, Bray MJ, Torstenson E, Jones S, Shrubsole MJ, Muff HJ, Hartmann KE. Nonsteroidal Anti-inflammatory Drug Interaction with Prostacyclin Synthase Protects from Miscarriage. Sci Rep. 2017 Aug 8/29/2017; 7(1): 9874. PMID: 28852049, PMCID: PMC5575303, PII: 10.1038/s41598-017-10150-2, DOI: 10.1038/s41598-017-10150-2, ISSN: 2045-2322. 


Adverse Pregnancy Outcome Studies with Other Resources


Velez Edwards DR, Likis FE, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck CJ, Nikki McKoy J, Hartmann KE. Progestogens for preterm birth prevention: a systematic review and meta-analysis by drug route. Archives of Gynecology and Obstetrics. 287: 1059-66. PMID 23532387 DOI: 10.1007/s00404-013-2789-9 

Likis FE, Edwards DR, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck CJ, McKoy JN, Hartmann KE. Progestogens for preterm birth prevention: a systematic review and meta-analysis. Obstet Gynecol. 2012 Oct; 120(4): 897-907. PMID: 22955308, DOI: 10.1097/AOG.0b013e3182699a15, ISSN: 1873-233X. 

Romero R, Friel LA, Velez Edwards DR, Kusanovic JP, Hassan SS, Mazaki-Tovi S, Vaisbuch E, Kim CJ, Erez O, Chaiworapongsa T, Pearce BD, Bartlett J, Salisbury BA, Anant MK, Vovis GF, Lee MS, Gomez R, Behnke E, Oyarzun E, Tromp G, Williams SM, Menon R. A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM). Am. J. Obstet. Gynecol [print-electronic]. 2010 Oct; 203(4): 361.e1-361.e30. PMID: 20673868, PMCID: PMC2989662, PII: S0002-9378(10)00669-1, DOI: 10.1016/j.ajog.2010.05.026, ISSN: 1097-6868.

Dolan SM, Hollegaard MV, Merialdi M, Betran AP, Allen T, Abelow C, Nace J, Lin BK, Khoury MJ, Ioannidis JP, Bagade S, Zheng X, Dubin RA, Bertram L, Velez Edwards DR, Menon R. Synopsis of preterm birth genetic association studies: the preterm birth genetics knowledge base (PTBGene). Public Health Genomics [print-electronic]. 2010; 13(7-8): 514-23. PMID: 20484876, PII: 000294202, DOI: 10.1159/000294202, ISSN: 1662-8063. 

Romero R, Velez Edwards DR, Kusanovic JP, Hassan SS, Mazaki-Tovi S, Vaisbuch E, Kim CJ, Chaiworapongsa T, Pearce BD, Friel LA, Bartlett J, Anant MK, Salisbury BA, Vovis GF, Lee MS, Gomez R, Behnke E, Oyarzun E, Tromp G, Williams SM, Menon R. Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes. Am. J. Obstet. Gynecol. 2010 May; 202(5): 431.e1-34. PMID: 20452482, PMCID: PMC3604889, PII: S0002-9378(10)00345-5, DOI: 10.1016/j.ajog.2010.03.026, ISSN: 1097-6868. 

Menon R, Fortunato SJ, Edwards DR, Williams SM. Association of genetic variants, ethnicity and preterm birth with amniotic fluid cytokine concentrations. Ann. Hum. Genet. 2010 Mar; 74(2): 165-83. PMID: 20369436, ISSN: 1469-1809

Ryckman KK, Morken NH, White MJ, Velez DR, Menon R, Fortunato SJ, Magnus P, Williams SM, Jacobsson B. Maternal and fetal genetic associations of PTGER3 and PON1 with preterm birth. PLoS ONE. 2010; 5(2): e9040. PMID: 20140262, PMCID: PMC2815792, DOI: 10.1371/journal.pone.0009040, ISSN: 1932-6203. 

Williams SM, Velez DR, Menon R. Geographic ancestry and markers of preterm birth. Expert Rev. Mol. Diagn. 2010 Jan; 10(1): 27-32. PMID: 20014920, DOI: 10.1586/erm.09.70, ISSN: 1744-8352. 

Menon R, Pearce B, Velez DR, Merialdi M, Williams SM, Fortunato SJ, Thorsen P. Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants. Reprod. Biol. Endocrinol. 2009; 7: 62. PMID: 19527514, PMCID: PMC2714850, PII: 1477-7827-7-62, DOI: 10.1186/1477-7827-7-62, ISSN: 1477-7827. 

Velez DR, Fortunato S, Thorsen P, Lombardi SJ, Williams SM, Menon R. Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants. Am. J. Obstet. Gynecol [print-electronic]. 2009 Feb; 200(2): 209.e1-27. PMID: 19019335, PII: S0002-9378(08)00987-3, DOI: 10.1016/j.ajog.2008.08.051, ISSN: 1097-6868.

Velez DR, Fortunato SJ, Thorsen P, Lombardi SJ, Williams SM, Menon R. Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. PLoS ONE. 2008; 3(9): e3283. PMID: 18818748, PMCID: PMC2553267, DOI: 10.1371/journal.pone.0003283, ISSN: 1932-6203.

Menon R, Velez DR, Morgan N, Lombardi SJ, Fortunato SJ, Williams SM. Genetic regulation of amniotic fluid TNF-alpha and soluble TNF receptor concentrations affected by race and preterm birth. Hum. Genet [print-electronic]. 2008 Oct; 124(3): 243-53. PMID: 18807256, DOI: 10.1007/s00439-008-0547-z, ISSN: 1432-1203. 

Fortunato SJ, Menon R, Velez DR, Thorsen P, Williams SM. Racial disparity in maternal-fetal genetic epistasis in spontaneous preterm birth. Am. J. Obstet. Gynecol. 2008 Jun; 198(6): 666.e1-9; discussion 666.e9. PMID: 18538149, PII: S0002-9378(08)00139-7, DOI: 10.1016/j.ajog.2008.02.003, ISSN: 1097-6868. 

Velez DR, Fortunato SJ, Morgan N, Edwards TL, Lombardi SJ, Williams SM, Menon R. Patterns of cytokine profiles differ with pregnancy outcome and ethnicity. Hum. Reprod [print-electronic]. 2008 Aug; 23(8): 1902-9. PMID: 18487217, PII: den170, DOI: 10.1093/humrep/den170, ISSN: 1460-2350. 

Velez DR, Fortunato SJ, Williams SM, Menon R. Interleukin-6 (IL-6) and receptor (IL6-R) gene haplotypes associate with amniotic fluid protein concentrations in preterm birth. Hum. Mol. Genet [print-electronic]. 2008 Jun 6/1/2008; 17(11): 1619-30. PMID: 18276608, PII: ddn049, DOI: 10.1093/hmg/ddn049, ISSN: 1460-2083. 

Velez DR, Menon R, Simhan H, Fortunato S, Canter JA, Williams SM. Mitochondrial DNA variant A4917G, smoking and spontaneous preterm birth. Mitochondrion [print-electronic]. 2008 Mar; 8(2): 130-5. PMID: 18082471, PII: S1567-7249(07)00253-X, DOI: 10.1016/j.mito.2007.10.007, ISSN: 1567-7249. 

Velez DR, Menon R, Thorsen P, Jiang L, Simhan H, Morgan N, Fortunato SJ, Williams SM. Ethnic differences in interleukin 6 (IL-6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels. Ann. Hum. Genet [print-electronic]. 2007 Sep; 71(Pt 5): 586-600. PMID: 17346257, PII: AHG352, DOI: 10.1111/j.1469-1809.2007.00352.x, ISSN: 0003-4800. 

Menon R, Velez DR, Thorsen P, Vogel I, Jacobsson B, Williams SM, Fortunato SJ. Ethnic differences in key candidate genes for spontaneous preterm birth: TNF-alpha and its receptors. Hum. Hered [print-electronic]. 2006; 62(2): 107-18. PMID: 17047334, PII: 96301, DOI: 10.1159/000096301, ISSN: 0001-5652. 

Menon R, Velez DR, Simhan H, Ryckman K, Jiang L, Thorsen P, Vogel I, Jacobsson B, Merialdi M, Williams SM, Fortunato SJ. Multilocus interactions at maternal tumor necrosis factor-alpha, tumor necrosis factor receptors, interleukin-6 and interleukin-6 receptor genes predict spontaneous preterm labor in European-American women. Am. J. Obstet. Gynecol. 2006 Jun; 194(6): 1616-24. PMID: 16731080, PII: S0002-9378(06)00382-6, DOI: 10.1016/j.ajog.2006.03.059, ISSN: 1097-6868.