{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:27:22Z","timestamp":1760243242162,"version":"build-2065373602"},"reference-count":22,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T00:00:00Z","timestamp":1399507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objective: To investigate whether maternal serum pregnancy associated plasma protein-A (PAPP-A), total \u03b2 human chorionic gonadotropin (hCG) levels and nuchal translucency (NT) measurements differ in women with pre-gestational diabetes mellitus (PGDM) compared to non-diabetic controls and to assess whether correction factors are needed for diabetic women in calculation of aneuploidy risks. Study Design: We performed a retrospective study of all women who underwent first trimester aneuploidy screening (11 + 0 to 13 + 6 weeks) from 2005 to 2011. The primary study outcome was the difference in PAPP-A, \u03b2-hCG and NT multiples of median between women with PGDM and non-diabetic women. Results: Of 6741 eligible patients, 103 patients with PGDM were using insulin and 4 patients were using oral hypoglycemic agents; the latter were excluded due to small number. There was 12% reduction of median PAPP-A (p = 0.001) and 18% reduction of median hCG (p = 0.006) in women with PGDM receiving insulin. There was no difference in NT. Conclusions: In women with PGDM receiving insulin, PAPP-A and  \u03b2-hCG levels are significantly lower compared to non-diabetic women. This suggests that when calculating risks for aneuploidy, correction factors should be considered to adjust PAPP-A and  \u03b2-hCG concentrations to those seen in non-diabetic women.<\/jats:p>","DOI":"10.3390\/jcm3020480","type":"journal-article","created":{"date-parts":[[2014,5,8]],"date-time":"2014-05-08T11:45:35Z","timestamp":1399549535000},"page":"480-490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["First Trimester Aneuploidy Screening Markers in Women with Pre-Gestational Diabetes Mellitus"],"prefix":"10.3390","volume":"3","author":[{"given":"Padmalatha","family":"Gurram","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Connecticut Health Center-School of Medicine, Farmington, CT 06032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Benn","sequence":"additional","affiliation":[{"name":"Department of Genetics and Developmental Biology, University of Connecticut Health  Center-School of Medicine, Farmington, CT 06032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Grady","sequence":"additional","affiliation":[{"name":"Biostatistics Center, Connecticut Institute for Clinical and Translational Science,  University of Connecticut Health Center-School of Medicine, Farmington, CT 06032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Marie","family":"Prabulos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Connecticut Health Center-School of Medicine, Farmington, CT 06032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winston","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Connecticut Health Center-School of Medicine, Farmington, CT 06032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/uog.5332","article-title":"First-trimester screening for trisomy 21 by free \u03b2-human chorionic gonadotropin and pregnancy-associated plasma protein-A: Impact of maternal and pregnancy characteristics","volume":"31","author":"Kagan","year":"2008","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1258\/jms.2009.009028","article-title":"Adjustment of serum markers in first trimester screening","volume":"16","author":"Palomaki","year":"2009","journal-title":"J. Med. Screen."},{"key":"ref_3","first-page":"1323","article-title":"Maternal serum-\u03b1-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Report of UK collaborative study on \u03b1-fetoprotein in relation to neural-tube defects","volume":"1","author":"Wald","year":"1977","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/S0140-6736(84)92389-4","article-title":"Maternal serum \u03b1-fetoprotein measurement: A screening test for Down\u2019s syndrome","volume":"1","author":"Cuckle","year":"1984","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/pd.994","article-title":"Second trimester prenatal serum markers for Down syndrome in women with insulin\u2014Dependent diabetes mellitus","volume":"24","author":"Huttley","year":"2004","journal-title":"Prenat. Diagn."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2008.02.046","article-title":"Maternal serum \u03b1-fetoprotein values in type 1 and type 2 diabetic patients","volume":"199","author":"Thornburg","year":"2008","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1053\/j.semperi.2005.05.004","article-title":"Down Syndrome Screening in the First and\/or Second Trimester: Model Predicted Performance Using Meta-Analysis Parameters","volume":"29","author":"Cuckle","year":"2005","journal-title":"Semin. Perinatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/pd.1229","article-title":"The influence of maternal insulin-dependent diabetes on fetal nuchal translucency thickness and first-trimester maternal serum biochemical markers of aneuploidy","volume":"25","author":"Spencer","year":"2005","journal-title":"Prenat. Diagn."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/pd.2589","article-title":"A re-evaluation of the influence of maternal insulin-dependent diabetes on fetal nuchal translucency thickness and first-trimester maternal serum biochemical markers of aneuploidy","volume":"30","author":"Spencer","year":"2010","journal-title":"Prenat. Diagn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1471-0528.2011.03253.x","article-title":"First trimester maternal serum free human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus","volume":"119","author":"Savvidou","year":"2012","journal-title":"BJOG"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1159\/000336252","article-title":"Temporal Effect of Afro-Caribbean Race on Serum Pregnancy-Associated Plasma Protein-A at 9\u201313 Weeks Gestation in Screening for Aneuploidies","volume":"31","author":"Ball","year":"2012","journal-title":"Fetal Diagn. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1002\/pd.1791","article-title":"The impact of bias in MoM values on patient risk and screening performance for Down syndrome","volume":"27","author":"Nix","year":"2007","journal-title":"Prenat. Diagn."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.2337\/dc07-1092","article-title":"Pregnancy-Associated Plasma Protein-A Levels are Related to Glycemic Control but Not to Lipid Profile or Hemostatic Parameters in Type 2 Diabetes","volume":"30","author":"Pellitero","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1600-0412.2011.01212.x","article-title":"Impact of type 1 diabetes and glycemic control on fetal aneuploidy biochemical markers","volume":"91","author":"Madsen","year":"2012","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/clinchem\/27.3.493","article-title":"A multi-rule Shewhart chart for quality control in clinical chemistry","volume":"27","author":"Westgard","year":"1981","journal-title":"Clin. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/pd.1188","article-title":"Maternal weight and ethnic adjustment within a first-trimester Down syndrome and trisomy 18 screening program","volume":"25","author":"Krantz","year":"2005","journal-title":"Prenat. Diagn."},{"key":"ref_17","unstructured":"Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences, Lawrence Earlbaum Associates. [2nd ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1056\/NEJMoa003147","article-title":"Pregnancy-associated plasma protein A as a marker of acute coronary syndromes","volume":"345","author":"Conover","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1073\/pnas.96.6.3149","article-title":"The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A","volume":"96","author":"Lawrence","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.2337\/db11-1488","article-title":"Insulin-Like Growth Factor Axis and Risk of Type 2 Diabetes in Women","volume":"61","author":"Rajpathak","year":"2012","journal-title":"Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1161\/01.RES.86.2.125","article-title":"The Insulin-Like Growth Factor Axis: A Review of Atherosclerosis and Restenosis","volume":"86","author":"Conover","year":"2000","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/pd.2733","article-title":"First trimester pregnancy-associated plasma protein-A in pregnancies complicated by subsequent gestational diabetes","volume":"31","author":"Beneventi","year":"2011","journal-title":"Prenat. 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