29 NOV 2010
Appendix
People contributing to the study at the six clinical centers:
Colorado Clinical Center: Katherine Barriga 12, Judith Baxter, 9,12 George Eisenbarth M. D., Ph.D., Patricia Gesualdo, 2,12,14, Michelle Hoffman, 12, 13, 14 Lisa Ide, Jill Norris, Ph. D., 2,12 and Kathleen Waugh, 7, 12 University of Colorado at Denver and Health Sciences Center, Barbara Davis Center for Childhood Diabetes.
Georgia/Florida Clinical Center: Jin-Xiong She, Ph.D.PI, 1,3,4,11 Andy Muir, M.D.^ 7, 13, Diane Hopkins, 12 Leigh Steed 12, Angela Choate, *12, Katherine Silvis, 2 Meena Shankar, *2 Yi-Hua Huang, Ph. D, Ping Yang, Hong-Jie Wang, Jessica Legget, Kim English, Richard IcIndoe, Ph. D., Angela Wilcox*, Michael Haller, M.D. *14 Medical College of Georgia, University of Florida and ^Emory University
German Clinical Center: Julia Bollwein, 2,12 Ezio Bonifacioa, Ph. D, *5, SandrHummer, Ph. D, 2 Mathilde Kersting, ¥ Stephanie Koenig, 2 Annette Knopff, 7 Lydia Rank, 2,12 Roswith Roth, Ph.D ^9, Stefanie Schoen, ¥ Petra Schewaiger,7 Wolfgang Sichert-Hellert, Ph. D., ¥2 , Christiane Winkler. 2,12 Diabetes Research Institute and *Center for Regenerative Therapies, TU Dresden, ^ Institute of Psychology, University of Graz, Austria, ¥ Research Institute for Child Nutrition, Dortmund.
Pennsylvania Satellite Center: Dorothy Becker, M. D., Margaret Franciscus, 12 MaryEllen Dalmagro-Elias, 2, Ashi Daftary, M. D. Children’s Hospital of Pittsburh of UPMC.
Finland Clinical Center: Kirsti Nanto-Salonen, M.D., Ph. D, ¥^12 Jorma Ilonen, M.D., Ph. D. ¥¶
,3 Mikael Knip, m.D., *± Riitta Veijola, M.D., μ¤Tuula Simell, Ph.D., ¥^9, 12 Heikki Hyöty, M.D., *±,6 Suvi M. Virtanen, M. D., Ph. D., *§,2 Carina Kronberg-Kippilä, §,2 Maija Torma, ¥^ 12, 14 Barbara Simell, ¥^ Eeva Ruohonen, ¥^, Minna Romo ¥^ Elina Mantymaki, ¥^ Tiina Niinien, *± Mia Nyblom, *± , Aino Stenius μ¤ ¥ University of Turku, * University of Tampere, μ University of Oulo, ^ Turku University Hospital, ± Tampere University Hospital, Oulo University Hospital and National Public Health Institute, Finland, ¶ University of Kuopio.
Sweden Clinical Center: Daniel Agardh, M. D., Ph. D. 13 Peter Almgren, Marie Andersson-Turpeinen, Carin Andrén-Aronsson, 2,13 Maria Ask, Ulla-Marie Carlsson, Corrado Cilio, 5 MD. Ph.D., Jenny Bremer, Lina Fransson, Emelie Ericsson-Hallström, Joanna Gerardsson, Barbro Gustavsson, Ulrika Gustavsson, Gertie Hansson, 12,14 Ida Hansson, Monica Hansen, Susanne Hyberg, Rasmus Håkansson, Sten Ivarsson, M. D., 6, Fredrik Johansen, Jesper Johansson, Helena Larsson, M. D., Ph. D., 14, Barbro Lernmark Ph. D., 9,12 Maria Markan, Jessica Melin, Maria Månsson Martinez, Anita Nilsson, Kerstin Pearson, Kobra Rahmati, Monica Sedig Järvirova, Birigtta Sjöberg, Anne Wallin, Ingrid Wigheden, Ǻsa Wimar, Lund University.
Washington Clinical Center: Peng Hui, M. D., Michael Brantley, 7,12 Claire Cowen Crouch, Kristen M. Hay,2 Stephen Ayres, Carla Hammar, Viktoria Steptikova, Jenn Skidmore, Bonnie Bang, Denise Mulenga, Nicholas Vanneman, 12 Judy Ewing, Isac, Whitaker Emily Wion. Pacific North West Research Institute.
New York Satellite Center: Robin S. Goland, M.D., Barney Softness, M. D., Ellen Greenberg, Diana Arnold, 12 Erica Arrecis2 Lee Trope12 Columbia University, Naomi Berrie Diabete Center.
Data Coordinating Center: Michael Abbondondolo, Lori Ballard, London Bounmananh, Rasheedah Brown, 12 David Cuthbertson, Christina Foster, Veena Gowda, Hye-Seung Lee, Ph. D., Shu Liu, Jamie Malloy, Cristina McCarthy, Wendy McLeod, 2,9 Lavanya Nallamshetty, Susan Smith, 12 Ulla Uusitalo, Ph. D., 2 Jimin Yang, Ph. D. 2 University of South Florida.
Other contributors: Thomas Briese, 6 Columbia University, Henry Erlich, 3 Childrens Hospital Oakland Research Insitute: Suzanne Bennett Johnson, 9, 12 Florida State University and Steve Oberste,6 Centers for Disease Control and Prevention.
Committees: 1Ancillary Studies, 2Diet, 3Genetics, 4Human Subjects/Publicity/Publications, 5Immune Markers, 6Infectious Agents, 7Laboratory Implementation. 8Maternal Studies, 9Psychosocial, 10Quality Assurance, Steering, 11Steering, 12Study Coordinators, 13Celiac Disease and 14Clinical Implementation.
Table 2. Birth weight and length by HLA types: Mean ± Standard Deviation (SD)(lower quartile, upper quartile)
DQ2/8 / DQ 8/8 / DQ 4/8 / DQ 2/2Overall / N / 2182 (40%) / 1094 (20%) / 1011 (19%) / 1174 (21%)
Birth weight / 3.53±0.50
(3.20,3.86) / 3.53±0.49
(3.20,3.86) / 3.51±0.49
(3.19,3.82) / 3.53±0.49
(3.23,3.86)
Birth length / 50.92±2.49
(49,53) / 50.87±2.51
(49,53) / 50.62±2.41
(49,52) / 50.93±2.51
(50,53)
US / N / 839(40%) / 431(20%) / 326(16%) / 507(24%)
Birth weight / 3.45±0.47
(3.12,3.74) / 3.44±0.46
(3.12,3.74) / 3.40±0.45
(3.15,3.69) / 3.44±0.48
(3.12,3.74)
Birth length / 51.08±2.80
(49,53) / 50.86±2.87
(48,53) / 50.68±2.79
(48,53) / 50.85±2.84
(50,53)
Finland / N / 394(18%) / 187(17%) / 397(39%) / 179(15%)
Birth weight / 3.56±0.49
(3.20,3.90) / 3.54±0.44
(3.24,3.86) / 3.54±0.50
(3.19,3.87) / 3.55±0.46
(3.27,3.84)
Birth length / 50.57±2.06
(49,52) / 50.66±2.02
(49,52) / 50.50±2.09
(49,52) / 50.56±2.15
(49,52)
Germany / N / 128(46%) / 51(18%) / 29(11%) / 69(25%)
Birth weight / 3.46±0.47
(3.14,3.75) / 3.37±0.45
(3.03,3.68) / 3.52±0.55
(3.25,3.78) / 3.49±0.46
(3.20,3.76)
Birth length / 51.68±2.49
(50,53) / 51.67±2.14
(50,53) / 52.24±2.87
(50,54) / 51.95±2.20
(50,53)
Sweden / N / 821(43%) / 425(22%) / 259(13%) / 419(22%)
Birth weight / 3.62±0.52
(3.30,3.95) / 3.64±0.51
(3.26,4.02) / 3.60±0.49
(3.27,3.90) / 3.64±0.51
(3.30,3.97)
Birth length / 50.82±2.32
(49,52) / 50.87±2.34
(49,52) / 50.56±2.22
(49,52) / 51.01±2.22
(50,52)
Table 3-1. HLA types: Univariate analysis: N (%) and Mean ± SD
Total / DQ 2/8 / DQ 8/8 / DQ 4/8 / DQ 2/2 / p
2182(40%)1 / 1094(20%) / 1011(19%) / 1174(21%)
Country / US / 839(38%) / 431(39%) / 326(32%) / 507(43%) / <.0001
Finland / 394(18%) / 187(17%) / 397(39%) / 179(15%)
Germany / 128(6%) / 51(5%) / 29(3%) / 69(6%)
Sweden / 821(38%) / 425(39%) / 259(26%) / 419(36%)
Sex / Female / 1087(50%) / 558(51%) / 496(49%) / 542(46%) / 0.1079
Male / 1095(50%) / 536(49%) / 515(51%) / 632(54%)
Gestational age(weeks) / 39.77±1.402 / 39.69±1.35 / 39.73±1.34 / 39.65±1.44 / 0.0979
1: N(%);2: Mean±SD
Table 3-2. Birth weight and length: Univariate analysis
N / Birth weight(kg) / p / Birth length(cm) / pDemographics
Country / US / 2103(39%)1 / 3.44±0.472 / <.0001 / 50.92±2.82 / <.0001
Finland / 1157(21%) / 3.55±0.48 / 50.56±2.07
Germany / 277(5%) / 3.46±0.47 / 51.81±2.40
Sweden / 1924(35%) / 3.63±0.51 / 50.83±2.29
Sex / Female / 2683(49%) / 3.47±0.48 / <.0001 / 50.40±2.45 / <.0001
Male / 2778(51%) / 3.59±0.50 / 51.30±2.44
Prenatal characteristics
Smoking during pregnancy / Unknown / 177(3%) / 3.54±0.46 / 50.88±2.70
No / 4595(84%) / 3.54±0.49 / <.0001 / 50.94±2.46 / <.0001
Yes / 689(13%) / 3.44±0.53 / 50.27±2.53
Alcohol consumption at trimester (per month) / Unknown / 191(3%) / 3.57±0.50 / 50.94±2.65
None / 4336(80%) / 3.53±0.50 / 0.722 / 50.81±2.49 / 0.022
1-2 drinks / 762(14%) / 3.53±0.48 / 51.08±2.44
>2 drinks / 172(3%) / 3.56±0.43 / 50.95±2.32
Any delivery complication / Unknown / 168(3%) / 3.57±0.51 / 50.91±2.68
No / 2845(52%) / 3.56±0.47 / <.0001 / 51.00±2.35 / <.0001
Yes / 2448(45%) / 3.48±0.52 / 50.69±2.61
Gestational age (weeks) / 5443 / 0.171(0.163,0.180)3 / <.0001 / 0.694(0.650,0.738) / <.0001
Parental physical characteristics
Mother age at birth (years) / 5461 / 0.006(0.004,0.009) / <.0001 / 0.028(0.015,0.040) / <.0001
Weight at the end of pregnancy (kg) / 5255 / 0.008(0.007,0.009) / <.0001 / 0.029(0.025,0.033) / <.0001
Mother height(cm) / 5328 / 0.016(0.014,0.018) / <.0001 / 0.071(0.061,0.080) / <.0001
Father height(cm) / 1495 / 0.008(0.005,0.012) / <.0001 / 0.050(0.034,0.067) / <.0001
1: N(%); 2: Mean±SD; 3: Regression parameter estimate (95% confidence interval)
Table 4-1. Birth weight and length with TEDDY HLA types: Multiple regression - Overall
Model
(N) / TEDDY HLA genotype / PE / SE / Pr|t| / PrF / PE / SE / Pr|t| / PrF
Model1
(5461) / AvsC / 0.020 / 0.019 / 0.280 / 0.717 / 0.303 / 0.095 / 0.001** / 0.009**
BvsC / 0.021 / 0.022 / 0.338 / 0.248 / 0.108 / 0.022**
DvsC / 0.018 / 0.021 / 0.385 / 0.306 / 0.107 / 0.004**
Model2
(5443) / AvsC / 0.009 / 0.017 / 0.599 / 0.498 / 0.156 / 0.086 / 0.070* / 0.190
BvsC / 0.021 / 0.019 / 0.257 / 0.181 / 0.099 / 0.066*
DvsC / 0.025 / 0.019 / 0.189 / 0.186 / 0.097 / 0.056*
Model3
(5096) / AvsC / 0.004 / 0.016 / 0.791 / 0.605 / 0.096 / 0.087 / 0.269 / 0.539
BvsC / 0.021 / 0.019 / 0.253 / 0.140 / 0.099 / 0.157
DvsC / 0.001 / 0.019 / 0.949 / 0.068 / 0.098 / 0.489
Model4
(1429) / AvsC / -0.035 / 0.030 / 0.256 / 0.383 / 0.159 / 0.156 / 0.311 / 0.606
BvsC / 0.002 / 0.035 / 0.947 / 0.200 / 0.178 / 0.260
DvsC / -0.041 / 0.034 / 0.230 / 0.050 / 0.176 / 0.777
PE: Multiple regression parameter estimate; SE: Standard error; Pr|t|: p-value for parameter estimate; PrF: p-value for Analysis of covariance; Model 1: Unadjusted; Model2: Adjusted for sex and gestational age; Model3: Additionally adjusted for mother characteristics (smoking, alcohol consumption at trimester, any delivery complication, age at the subject’s birth, height and weight at the end of the pregnancy); Model4: Additionally adjusted for father height.; **:p<0.05; *:p<0.1
Table 4-2. Birth weight and length with TEDDY HLA types: Multiple regression – By Country
Country / Model
(N) / TEDDY HLA genotype / PE / SE / Pr|t| / PrF / PE / SE / Pr|t| / PrF
US / Model1
(2103) / AvsC / 0.046 / 0.031 / 0.134 / 0.488 / 0.403 / 0.184 / 0.029** / 0.130
BvsC / 0.042 / 0.034 / 0.223 / 0.185 / 0.207 / 0.371
DvsC / 0.042 / 0.033 / 0.209 / 0.169 / 0.200 / 0.400
Model2
(2092) / AvsC / 0.045 / 0.027 / 0.099* / 0.172 / 0.391 / 0.172 / 0.023** / 0.151
BvsC / 0.050 / 0.031 / 0.106 / 0.230 / 0.194 / 0.236
DvsC / 0.065 / 0.030 / 0.028** / 0.239 / 0.188 / 0.202
Model3
(1928) / AvsC / 0.016 / 0.028 / 0.575 / 0.587 / 0.188 / 0.181 / 0.300 / 0.638
BvsC / 0.036 / 0.031 / 0.240 / 0.072 / 0.202 / 0.720
DvsC / 0.033 / 0.030 / 0.279 / 0.031 / 0.197 / 0.873
Model4
(487) / AvsC / -0.015 / 0.053 / 0.779 / 0.699 / 0.085 / 0.346 / 0.806 / 0.835
BvsC / 0.040 / 0.059 / 0.498 / 0.249 / 0.383 / 0.516
DvsC / -0.008 / 0.058 / 0.890 / -0.053 / 0.379 / 0.889
Finland / Model1
(1157) / AvsC / 0.016 / 0.034 / 0.644 / 0.948 / 0.068 / 0.148 / 0.645 / 0.845
BvsC / -0.006 / 0.043 / 0.879 / 0.165 / 0.184 / 0.370
DvsC / 0.001 / 0.043 / 0.985 / 0.065 / 0.187 / 0.728
Model2
(1156) / AvsC / 0.005 / 0.031 / 0.868 / 0.998 / 0.013 / 0.131 / 0.922 / 0.611
BvsC / -0.001 / 0.038 / 0.977 / 0.206 / 0.163 / 0.206
DvsC / 0.000 / 0.039 / 0.992 / 0.068 / 0.166 / 0.682
Model3
(1102) / AvsC / 0.011 / 0.031 / 0.713 / 0.959 / 0.001 / 0.129 / 0.995 / 0.685
BvsC / -0.001 / 0.038 / 0.986 / 0.178 / 0.160 / 0.267
DvsC / -0.009 / 0.039 / 0.826 / 0.055 / 0.164 / 0.738
Model4
(231) / AvsC / -0.072 / 0.066 / 0.278 / 0.511 / -0.047 / 0.278 / 0.866 / 0.888
BvsC / -0.093 / 0.080 / 0.246 / -0.234 / 0.337 / 0.488
DvsC / -0.102 / 0.085 / 0.230 / 0.051 / 0.357 / 0.886
Germany / Model1
(277) / AvsC / -0.056 / 0.098 / 0.563 / 0.461 / -0.560 / 0.495 / 0.259 / 0.633
BvsC / -0.148 / 0.110 / 0.181 / -0.577 / 0.560 / 0.303
DvsC / -0.026 / 0.105 / 0.807 / -0.290 / 0.532 / 0.586
Model2
(276) / AvsC / -0.068 / 0.084 / 0.420 / 0.245 / -0.568 / 0.459 / 0.217 / 0.520
BvsC / -0.153 / 0.095 / 0.107 / -0.585 / 0.519 / 0.261
DvsC / -0.015 / 0.090 / 0.872 / -0.246 / 0.492 / 0.617
Model3
(254) / AvsC / -0.049 / 0.087 / 0.573 / 0.609 / -0.276 / 0.476 / 0.562 / 0.938
BvsC / -0.121 / 0.098 / 0.216 / -0.305 / 0.533 / 0.568
DvsC / -0.054 / 0.093 / 0.566 / -0.302 / 0.509 / 0.554
Model4
(N=76) / AvsC / -0.066 / 0.139 / 0.638 / 0.756 / -0.302 / 0.690 / 0.663 / 0.897
BvsC / -0.095 / 0.168 / 0.573 / -0.371 / 0.834 / 0.658
DvsC / 0.035 / 0.148 / 0.813 / 0.049 / 0.734 / 0.947
Sweden / Model1
(1924) / AvsC / 0.016 / 0.037 / 0.664 / 0.717 / 0.259 / 0.163 / 0.112 / 0.091*
BvsC / 0.039 / 0.040 / 0.329 / 0.313 / 0.181 / 0.083*
DvsC / 0.035 / 0.041 / 0.386 / 0.455 / 0.181 / 0.012**
Model2
(1919) / AvsC / -0.016 / 0.031 / 0.609 / 0.421 / 0.113 / 0.138 / 0.410 / 0.237
BvsC / 0.028 / 0.035 / 0.423 / 0.253 / 0.152 / 0.096*
DvsC / -0.006 / 0.035 / 0.860 / 0.254 / 0.153 / 0.096*
Model3
(1812) / AvsC / 0.001 / 0.030 / 0.971 / 0.172 / 0.138 / 0.135 / 0.308 / 0.319
BvsC / 0.042 / 0.033 / 0.209 / 0.276 / 0.150 / 0.066*
DvsC / -0.022 / 0.034 / 0.509 / 0.170 / 0.150 / 0.257
Model4
(635) / AvsC / 0.010 / 0.049 / 0.845 / 0.515 / 0.495 / 0.216 / 0.023** / 0.101
BvsC / 0.057 / 0.056 / 0.304 / 0.487 / 0.244 / 0.046**
DvsC / -0.016 / 0.055 / 0.778 / 0.261 / 0.241 / 0.280
PE: Multiple regression parameter estimate; SE: Standard error; Pr|t|: p-value for parameter estimate; PrF: p-value for Analysis of covariance; Model 1: Unadjusted; Model2: Adjusted for country, sex and gestational age; Model3: Additionally adjusted for mother characteristics (smoking, alcohol consumption at trimester, any delivery complication, age at the subject’s birth, height and weight at the end of the pregnancy); Model4: Additionally adjusted for father height.; **:p<0.05; *:p<0.1