The University of Manchester Research Maternal Glycemia During Pregnancy and Childhood Adiposity in the Hyperglycaemia and Adverse Pregnancy Outcome Follow-Up Study DOI: 10.1007/s00125-018-4809-6 Document Version Accepted author manuscript Link to publication record in Manchester Research Explorer Citation for published version (APA): Clayton, P., & et al. (2019). Maternal Glycemia During Pregnancy and Childhood Adiposity in the Hyperglycaemia and Adverse Pregnancy Outcome Follow-Up Study. Diabetologia, 62(4), 598-610. https://doi.org/10.1007/s00125- 018-4809-6 Published in: Diabetologia Citing this paper Please note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscript or Proof version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version. General rights Copyright and moral rights for the publications made accessible in the Research Explorer are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Takedown policy If you believe that this document breaches copyright please refer to the University of Manchester’s Takedown Procedures [http://man.ac.uk/04Y6Bo] or contact [email protected] providing relevant details, so we can investigate your claim. Download date:06. Jun. 2022
67
Embed
Maternal Glycemia During Pregnancy and Childhood Adiposity ...
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
The University of Manchester Research
Maternal Glycemia During Pregnancy and ChildhoodAdiposity in the Hyperglycaemia and Adverse PregnancyOutcome Follow-Up StudyDOI:10.1007/s00125-018-4809-6
Document VersionAccepted author manuscript
Link to publication record in Manchester Research Explorer
Citation for published version (APA):Clayton, P., & et al. (2019). Maternal Glycemia During Pregnancy and Childhood Adiposity in the Hyperglycaemiaand Adverse Pregnancy Outcome Follow-Up Study. Diabetologia, 62(4), 598-610. https://doi.org/10.1007/s00125-018-4809-6
Published in:Diabetologia
Citing this paperPlease note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscriptor Proof version this may differ from the final Published version. If citing, it is advised that you check and use thepublisher's definitive version.
General rightsCopyright and moral rights for the publications made accessible in the Research Explorer are retained by theauthors and/or other copyright owners and it is a condition of accessing publications that users recognise andabide by the legal requirements associated with these rights.
Takedown policyIf you believe that this document breaches copyright please refer to the University of Manchester’s TakedownProcedures [http://man.ac.uk/04Y6Bo] or contact [email protected] providingrelevant details, so we can investigate your claim.
in Obesity and Gestational Diabetes: Spotlight on Lipids. Curr Diab Rep 18: 37
[39] Jacob S, Nodzenski M, Reisetter AC, et al. (2017) Targeted Metabolomics
Demonstrates Distinct and Overlapping Maternal Metabolites Associated With BMI, Glucose,
and Insulin Sensitivity During Pregnancy Across Four Ancestry Groups. Diabetes Care 40: 911-
919
[40] Freinkel N (1980) Banting Lecture 1980. Of pregnancy and progeny. Diabetes 29: 1023-
1035
[41] Hawkes CP, Hourihane JO, Kenny LC, Irvine AD, Kiely M, Murray DM (2011) Gender-
and gestational age-specific body fat percentage at birth. Pediatrics 128: e645-651
[42] Regnault N, Gillman MW, Rifas-Shiman SL, Eggleston E, Oken E (2013) Sex-specific
associations of gestational glucose tolerance with childhood body composition. Diabetes Care
36: 3045-3053
[43] Krishnaveni GV, Veena SR, Hill JC, Kehoe S, Karat SC, Fall CH (2010) Intrauterine
exposure to maternal diabetes is associated with higher adiposity and insulin resistance and
clustering of cardiovascular risk markers in Indian children. Diabetes Care 33: 402-404
Table 1. Characteristics of Mothers during HAPO Pregnancy OGTT and their Children at Follow-
Up
Characteristics - Mothers
During HAPO Pregnancy
N=4832
Mean (SD)
Age at OGTT (yrs) 29.9 (5.7)
Gestational Age at OGTT (wks) 27.7 (1.7)
Height (cm) 161.8 (6.8)
Weight (kg) 72.0 (14.2)
Body Mass Index (BMI) (kg/m2) 27.5 (4.9)
Mean Arterial Pressure (mmHg) 80.5 (8.0)
Fasting Glucose (mmol/l) 4.5 (0.4)
1 h Glucose (mmol/l) 7.4 (1.7)
2 h Glucose (mmol/l) 6.1 (1.3)
HbA1c (mmol/l) 29.0 (4.5)
HbA1c (%) 4.8 (0.4)
N (%)
Race/Ethnicity
White, Non-Hispanic, n (%) 2287 (47.3)
Hispanic, n (%) 507 (10.5)
Black, Non-Hispanic, n (%) 775 (16.0)
Asian, n (%) 1176 (24.3)
Other, n (%) 87 (1.8)
Any Prenatal Smoking, n (%) 245 (5.1)
Any Prenatal Alcohol Use, n (%) 406 (8.4)
Parity (any prior delivery > 20 weeks),
n (%)
2485 (51.4)
Family History of Diabetes, n (%) 1077 (22.3)
Characteristics - Children Mean (SD)
At Follow-Up
Age (yrs) 11.4 (1.2)
Height (cm) 148.6 (10.2)
Weight (kg) 43.2 (13.3)
N (%)
Sex – Female, n (%) 2367 (49.0)
Tanner Stage - Girls
1, n (%) 381 (19.0)
2/3, n (%) 853 (42.5)
4/5, n (%) 774 (38.5)
Tanner Stage - Boys
1, n (%) 565 (36.0)
2/3, n (%) 726 (46.2)
4/5, n (%) 279 (17.8)
Table 2. Associations of Continuous Measures of Maternal Glucose and HbA1c During Pregnancy with Dichotomous Adiposity Outcomes among Children at Follow-up
Predictor Model 1 Model 2 Model 3 Model 4
OR (95% CI) p-valuea C-statistic OR (95% CI) p-valuea C-
statistic OR (95% CI) p-valuea C-statistic OR (95% CI) p-valuea C-
HbA1c 1.25 (1.15-1.37) <0.001*** 0.52 1.26 (1.15-1.38) <0.001*** 0.59 1.24 (1.13-1.36) <0.001*** 0.63 1.15 (1.05-1.26) 0.004** 0.67 a, 85th percentiles were determined using quantile regression adjusted for age, sex, and field center.
ap value from logistic regression model; * p<0.05, ** p<0.01, *** p<0.001
IOTF = International Obesity Task Force
Odds ratios for the dichotomous outcomes are for the continuous predictors higher by 1 standard deviation estimated in the original HAPO data: Fasting glucose – 0.4 mmol/l; 1 h glucose – 1.7 mmol/l; 2 h glucose – 1.3 mmol/l; HbA1c – 5.0 mmol/mol (0.45 %). Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
Table 3. Associations of Continuous Measures of Maternal Glucose and HbA1c During Pregnancy with Continuous Adiposity Outcomes among Children at Follow-up
ap value from linear regression model; * p<0.05, ** p<0.01, *** p<0.001
Beta estimates represent change in each continuous outcome for the continuous predictors higher by 1 standard deviation estimated in the original HAPO data: Fasting glucose – 0.4 mmol/l; 1 h glucose – 1.7 mmol/l; 2 h glucose – 1.3 mmol/l; HbA1c – 5.0 mmol/mol (0.45 %). Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1 + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
Table 4. Sex-Specific Fully Adjusted Associations of Continuous Measures of Maternal Glucose and HbA1c During Pregnancy with Dichotomous Adiposity Outcomes among Children at Follow-up
Predictor Boys Girls Interaction term p-valued OR (95% CI) p-valueb C-statistic OR (95% CI) p-valuec C-statistic
Odds ratios for the dichotomous outcomes are for the continuous predictors higher by 1 standard deviation estimated in the original HAPO data: Fasting glucose – 0.4 mmol/l; 1 h glucose – 1.7 mmol/l; 2 h glucose – 1.3 mmol/l; HbA1c – 5.0 mmol/mol (0.45 %). Models are adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, child pubertal status (Tanner Stage 1, 2/3, 4/5), maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age, maternal BMI during pregnancy.
a, 85th percentiles were determined using quantile regression adjusted for age, sex, and field center.
b p value from regression model for boys only; * p<0.05, ** p<0.01
c p-value from regression model for girls only; * p<0.05, ** p<0.01
d p-value for sex x maternal predictor interaction term from regression model including boys and girls; ** p<0.01
Table 5. Sex-Specific Fully Adjusted Associations of Continuous Measures of Maternal Glucose and A1c During Pregnancy with Continuous Adiposity Outcomes among Children at Follow-up
Predictor Boys Girls Interaction term p-valuec Beta (95% CI) p-valuea Adjusted R2 Beta (95% CI) p-valueb Adjusted R2
BMI z-score Fasting glucose -0.005 (-0.06-0.05) 0.84 0.17 0.007 (-0.04-0.06) 0.77 0.31 0.92 1-h glucose 0.02 (-0.03-0.07) 0.46 0.17 0.01 (-0.03-0.06) 0.56 0.31 0.46 2-h glucose 0.02 (-0.03-0.07) 0.45 0.17 0.02 (-0.03-0.06) 0.44 0.31 0.35 HbA1c 0.03 (-0.02-0.09) 0.22 0.23 0.04 (-0.009-0.09) 0.10 0.37 0.61 BOD POD % Fat Fasting glucose 0.37 (-0.10-0.83) 0.12 0.16 0.53 (0.11-0.94) 0.01* 0.23 0.51 1-h glucose 0.73 (0.29-1.17) 0.001** 0.16 0.49 (0.09-0.89) 0.02* 0.23 0.08 2-h glucose 0.69 (0.25-1.14) 0.002** 0.16 0.31 (-0.09-0.70) 0.13 0.23 0.005** HbA1c 0.33 (-0.15-0.80) 0.18 0.23 0.15 (-0.28-0.59) 0.49 0.29 0.52 Waist circumference (cm) Fasting glucose 0.12 (-0.37-0.60) 0.63 0.22 0.35 (-0.10-0.81) 0.13 0.35 0.85 1-h glucose 0.43 (-0.03-0.89) 0.07 0.23 0.44 (0.0002-0.87) 0.05 0.35 0.28 2-h glucose 0.51 (0.04-0.97) 0.03* 0.23 0.39 (-0.04-0.82) 0.07 0.35 0.11 HbA1c 0.41 (-0.08-0.90) 0.10 0.30 0.37 (-0.10-0.85) 0.13 0.41 0.79 Sum of Skinfolds (mm) Fasting glucose 0.60 (-0.39-1.59) 0.24 0.12 1.36 (0.48-2.24) 0.002** 0.18 0.53 1-h glucose 0.89 (-0.05-1.83) 0.06 0.12 0.97 (0.13-1.81) 0.02* 0.18 0.34 2-h glucose 0.98 (0.03-1.93) 0.04* 0.12 0.92 (0.09-1.76) 0.03* 0.18 0.14 HbA1c 1.09 (0.09-2.10) 0.03* 0.20 0.51 (-0.42-1.43) 0.28 0.25 0.42 Beta estimates represent change in each continuous outcome for the continuous predictors higher by 1 standard deviation estimated in the original HAPO data: Fasting glucose – 0.4 mmol/l; 1 h glucose – 1.7 mmol/l; 2 h glucose – 1.3 mmol/l; HbA1c – 5.0 mmol/mol (0.45 %). Models are adjusted for field center, child pubertal status (Tanner Stage 1, 2/3, 4/5), maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age, maternal BMI during pregnancy.
a p value from regression model for boys only; * p<0.05, ** p<0.01
b p-value from regression model for girls only; * p<0.05, ** p<0.01
c p-value for sex x maternal predictor interaction term from regression model including boys and girls; ** p<0.01
FIGURE LEGENDS
Figure 1 Flowchart describing enrollment for HAPO FUS.
HAPO Follow-Up Study Cooperative Research Group
Field Center Principal Investigators and Study Staff:
Bangkok C Deerochanawong, T Tanaphonpoonsuk (Rajavithi Hospital), S Binratkaew U
Chotigeat, W Manyam, (Queen Sirikit National Institute of Child Health)
Barbados M Forde, A Greenidge, K Neblett, PM Lashley, D Walcott (Queen Elizabeth
Hospital/School of Clinical Medicine and Research, University of the West Indies, Barbados)
Belfast K Corry, L Francis, J Irwin, A Langan, DR McCance, M Mousavi, (Belfast Health and
Social Care Trust), IS Young (Queen’s University Belfast)
Bellflower J Gutierrez, J Jimenez, JM Lawrence, DA Sacks, HS Takhar, E Tanton (Kaiser
Permanente Southern California)
Chicago WJ Brickman, J Howard, JL Josefson, L Miller, R Steuer (Ann and Robert H Lurie
Children’s Hospital/Northwestern University Feinberg School of Medicine)
Cleveland J Bjaloncik, PM Catalano, A Davis, K Koontz, L Presley, S Smith, A Tyhulski
(MetroHealth Medical Center/Case Western Reserve University)
Hong Kong A Li, RC Ma, R Ozaki, WH Tam, M Wong, C Yuen (The Chinese University of
Hong Kong/Prince of Wales Hospital)
Manchester PE Clayton, A Khan, A Vyas (Royal Manchester Children’s Hospital, Manchester
University Hospitals NHS Foundation Trust, Manchester Academic Healthy Sciences
Centre/School of Medical Sciences, Faculty of Biology, Medicine & Health, University of
Manchester), M Maresh (St. Mary’s Hospital, Central Manchester University Hospitals NHS
Foundation Trust, Manchester Academic Health Sciences Centre)
Petah-Tiqva H Benzaquen, N Glickman, A Hamou, O Hermon, O Horesh, Y Keren, , S Shalitin
(Schneider Children’s Medical Center of Israel), Y Lebenthal (Jesse Z and Sara Lea Shafer
Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider
Children’s Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University)
Toronto K Cordeiro, J Hamilton, HY Nguyen, S Steele (The Hospital for Sick Children,
University of Toronto)
Coordinating Centers: F Chen, AR Dyer, W Huang, A Kuang, M Jimenez, LP Lowe, WL
Lowe, Jr, BE Metzger, M Nodzenski, A Reisetter, D Scholtens, P Yim (Northwestern University
Feinberg School of Medicine)
Consultants: D Dunger, A Thomas
NIDDK: M Horlick, B Linder, A Unalp-Arida
NICHD: G Grave
15,812 eligible for HAPO FUS
9322 contacted
6490 unable to contact
4834HAPO FUS visits
4488 declinedparticipation
4832 physicalmeasurementsand/or glucoseoutcome data
2 excluded(non-fastingor unable to complete visitdue to autism)
[1] Jasuja GK, Travison TG, Davda M, Murabito JM, Basaria S, Zhang A, Kushnir MM, Rockwood AL, Meikle W, Pencina MJ, Coviello A, Rose AJ, D’Agostino R, Ramachandran SV, Bhasin S. (2013) Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study. The Journals of Gerontology: Series A. 68(6): 733-740.
[2] Bhasin S, Pencina M, Jasuja GK, Travison TG, Coviello A, Orwoll E, Wang PY, Nielson C, Wu F, Tajar A, Labrie F, Vesper H, Zhang A, Ulloor J, Singh R, D’Agostino R, Vasan RS. (2011) Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts. Journal of Clinical Endocrinology and Metabolism. 96(8):2430-2439.
ESM Table 1. Characteristics of HAPO FUS Participants and Non-Participants
HAPO Maternal Characteristics Participants N=4832
Non-Participants N=10980
Participants N=4832
Non-Participants N=10980
Unweighted Summaries Weighted Summaries* Mean (SD) Mean (SD) Mean (SD) Mean (SD) Age at OGTT(yrs) 29.9 (5.7) 29.1 (5.7) 30.0 (5.1) 29.1 (5.3) Body Mass Index (BMI) 27.5 (4.9) 27.5 (5.1) 27.5 (4.6) 27.5 (4.7) Height (cm) 161.8 (6.8) 160.7 (7.3) 161.1 (6.2) 160.9 (6.3) Fasting Plasma Glucose (mmol/l) 4.5 (0.4) 4.5 (0.4) 4.5 (0.4) 4.5 (0.4) 1-hr Plasma Glucose (mmol/l) 7.4 (1.7) 7.5 (1.7) 7.5 (1.7) 7.5 (1.7) 2-hr Plasma Glucose (mmol/l) 6.1 (1.3) 6.2 (1.3) 6.2 (1.3) 6.2 (1.3) HbA1c (mmol/mol) [%] 29.0 (4.5) [4.8
* Weighted summaries are weighted means and standard deviations or weighted percentages based on field-center-specific summary statistics with weights proportional to the total eligible population at the field center. **GDM=gestational diabetes mellitus defined by IADPSG criteria (1 or more glucose values from a 75g OGTT equals or exceeds FPG 5.1 mmol/l, 1-hr 10.0 mmol/l, 2-hr 8.5 mmol/l)
ESM Table 2. Frequencies of Child Adiposity at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
IOTF Overweight/Obesity IOTF Obesity BOD POD % Fat
* 85th percentiles were determined using quantile regression adjusted for age, sex, and field center.
IOTF = International Obesity Task Force
% is the proportion in the category with the adiposity outcome, n is the number in the category with the adiposity outcome, Total N is the total number in the category.
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
ESM Table 3. Frequencies and Odds Ratios of Child IOTF Overweight/Obesity at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
* 85th percentiles were determined using quantile regression adjusted for age, sex, and field center.
IOTF = International Obesity Task Force
% is the proportion in the category with the adiposity outcome, n is the number in the category with the adiposity outcome, Total N is the total number in the category.
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Odds ratios for the dichotomous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Table 4. Frequencies and Odds Ratios of Child IOTF Obesity at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
* 85th percentiles were determined using quantile regression adjusted for age, sex, and field center.
IOTF = International Obesity Task Force
% is the proportion in the category with the adiposity outcome, n is the number in the category with the adiposity outcome, Total N is the total number in the category.
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Odds ratios for the dichotomous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Table 5. Frequencies and Odds Ratios of Child BOD POD % Fat >85th percentile at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
> 37 [> 5.5] 25.4 (50/197) 2.62 (1.75-3.88) 2.41 (1.62-3.59) 2.26 (1.51-3.40) 1.80 (1.18-2.73) * 85th percentiles were determined using quantile regression adjusted for age, sex, and field center.
IOTF = International Obesity Task Force
% is the proportion in the category with the adiposity outcome, n is the number in the category with the adiposity outcome, Total N is the total number in the category.
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Odds ratios for the dichotomous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Table 6. Frequencies and Odds Ratios of Child Waist Circumference >85th percentile at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
* 85th percentiles were determined using quantile regression adjusted for age, sex, and field center.
IOTF = International Obesity Task Force
% is the proportion in the category with the adiposity outcome, n is the number in the category with the adiposity outcome, Total N is the total number in the category.
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Odds ratios for the dichotomous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Table 7. Frequencies and Odds Ratios of Child Sum of Skinfolds >85th percentile at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
* 85th percentiles were determined using quantile regression adjusted for age, sex, and field center.
IOTF = International Obesity Task Force
% is the proportion in the category with the adiposity outcome, n is the number in the category with the adiposity outcome, Total N is the total number in the category.
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Odds ratios for the dichotomous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Table 8. Mean (SD) of Continuous Measures of Child Adiposity at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
ESM Table 9. Group Means and Adjusted Mean Differences for Child BMI z-scores at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Adjusted mean differences for the continuous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean rterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Table 10. Group Means and Adjusted Mean Differences for Child BOD POD % Fat at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Adjusted mean differences for the continuous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Table 11. Group Means and Adjusted Mean Differences for Child Waist Circumference at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Adjusted mean differences for the continuous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Table 12. Group Means and Adjusted Mean Differences for Child Sum of Skinfolds at Follow-Up by Maternal Levels of Glucose and HbA1c During Pregnancy
The lowest three categories for FPG, 1-h PG and 2-h PG were used for analyses of glucose levels during the original HAPO Study; the fourth category includes values up to the fifth category for each measure that correspond to IADPSG diagnostic thresholds for GDM. For HbA1c, the lowest three categories were used for analyses of HbA1c levels during the original HAPO Study, and the fourth and fifth categories combine smaller categories used for original analyses of HbA1c.
Adjusted mean differences for the continuous outcomes are for each category relative to the lowest category. Model 1: Adjusted for field center for IOTF overweight/obesity and IOTF obesity outcomes, unadjusted for BOD POD % fat, waist circumference and sum of skinfolds >85th percentile outcomes; Model 2: Model 1+ + child pubertal status (Tanner Stage 1, 2/3, 4/5, sex x Tanner stage interaction), Model 3: Model 2 + maternal variables during pregnancy OGTT (age, height, any family history of diabetes, mean arterial pressure, parity (0, 1+), smoking (yes/no), alcohol (yes/no), gestational age). Model 4: Model 3 + maternal BMI during pregnancy.
ESM Figure 1
Frequencies of child a) overweight/obesity, b) obesity, c) percent bodyfat > 85th percentile, d) waist circumference > 85th percentile and e) sum of skinfolds > 85th percentile across categories of maternal fasting glucose (light orange lines), 1-h glucose (blue lines), 2-h glucose (red lines) and HbA1c (purple lines). Glucose categories are defined as follows: fasting plasma glucose level — category 1, less than 4.2 mmol per liter; category 2, 4.2 to 4.4 mmol per liter; category 3, 4.5 to 4.7 mmol per liter; category 4, 4.8 to 5.0 mmol per liter; category 5, 5.1 mmol per liter or more; 1-hour plasma glucose level — category 1, 5.8 mmol per liter or less; category 2, 5.9 to 7.3 mmol per liter; category 3, 7.4 to 8.6 mmol per liter; category 4, 8.7 to 9.9 mmol per liter; category 5, 10.0 mmol per liter or more; and 2-hr plasma glucose level — category 1, 5.0 mmol per liter or less; category 2, 5.1 to 6.0 mmol per liter; category 3, 6.1 to 6.9 mmol per liter; category 4, 7.0 to 8.4 mmol per liter; category 5, 8.5 mmol per liter or more. The key applies to all panels of the figure.
ESM Figure 2
Odds ratios and 95% confidence intervals in fully adjusted models including maternal BMI during pregnancy (Model 4) for child a) overweight/obesity, b) obesity, c) percent bodyfat > 85th percentile, d) waist circumference > 85th percentile and e) sum of skinfolds > 85th percentile for category 2 v. 1 (light orange lines), category 3 v. 1 (blue lines), category 4 v. 1 (red lines) and category 5 v. 1 (purple lines). Glucose categories are defined as follows: fasting plasma glucose level — category 1, less than 4.2 mmol per liter; category 2, 4.2 to 4.4 mmol per liter; category 3, 4.5 to 4.7 mmol per liter; category 4, 4.8 to 5.0 mmol per liter; category 5, 5.1 mmol per liter or more; 1-hour plasma glucose level — category 1, 5.8 mmol per liter or less; category 2, 5.9 to 7.3 mmol per liter; category 3, 7.4 to 8.6 mmol per liter; category 4, 8.7 to 9.9 mmol per liter; category 5, 10.0 mmol per liter or more; and 2-hr plasma glucose level — category 1, 5.0 mmol per liter or less; category 2, 5.1 to 6.0 mmol per liter; category 3, 6.1 to 6.9 mmol per liter; category 4, 7.0 to 8.4 mmol per liter; category 5, 8.5 mmol per liter or more. The key applies to all panels of the figure.
ESM Figure 3
Means of child a) BMI z-score, b) percent bodyfat, c) waist circumference and d) sum of skinfolds across categories of maternal fasting glucose (red lines), 1-h glucose (green lines), 2-h glucose (blue lines) and A1c (purple lines). Glucose categories are defined as follows: fasting plasma glucose level — category 1, less than 4.2 mmol per liter; category 2, 4.2 to 4.4 mmol per liter; category 3, 4.5 to 4.7 mmol per liter; category 4, 4.8 to 5.0 mmol per liter; category 5, 5.1 mmol per liter or more; 1-hour plasma glucose level — category 1, 5.8 mmol per liter or less; category 2, 5.9 to 7.3 mmol per liter; category 3, 7.4 to 8.6 mmol per liter; category 4, 8.7 to 9.9 mmol per liter; category 5, 10.0 mmol per liter or more; and 2-hr plasma glucose level — category 1, 5.0 mmol per liter or less; category 2, 5.1 to 6.0 mmol per liter; category 3, 6.1 to 6.9 mmol per liter; category 4, 7.0 to 8.4 mmol per liter; category 5, 8.5 mmol per liter or more. The key applies to all panels of the figure.