Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism
Authors: Scholtens Denise M. , Kuang Alan , Lowe Lynn P. , Hamilton Jill , Lawrence Jean M. , Lebenthal Yael , Brickman Wendy J. , Clayton Peter , Ma Ronald C. , McCance David , Tam Wing Hung , Catalano Patrick M. , Linder Barbara , Dyer Alan R. , Lowe William L. , Metzger Boyd E. ,   HAPO Follow-Up Study Cooperative Research Group, Deerochanawong Chaicharn , Tanaphonpoonsuk Thadchanan , Chotigeat Sukeeta Binratkaew Uraiwan , Manyam Wanee , Forde Martinette , Greenidge Andre , Neblett Kathleen , Lashley Paula Michele , Walcott Desiree , Corry Katie , Francis Loraine , Irwin Jo-anne , Langan Anne , McCance David R. , Mousavi Maureen , Young Ian , Gutierrez Jennifer , Jimenez Jennifer , Lawrence Jean M. , Sacks David A. , Takhar Harpreet S. , Tanton Elizabeth , Brickman Wendy J. , Howard Jennifer , Josefson Jami L. , Miller Lauren , Bjaloncik Jacqui , Catalano Patrick M. , Davis Ajuah , Koontz Michaela , Presley Larraine , Smith Shoi , Tyhulski Amanda , Li Albert Martin , Ma Ronald C. , Ozaki Risa , Tam Wing Hung , Wong Michelle , Yuen Cindy Siu Man , Clayton Peter E. , Khan Aysha , Vyas Avni , Maresh Michael , Benzaquen Hadasse , Glickman Naama , Hamou Alona , Hermon Orna , Horesh Orit , Keren Yael , Lebenthal Yael , Shalitin Shlomit , Cordeiro Kristina , Hamilton Jill , Nguyen Hahn Y. , Steele Shawna , Chen Fei , Dyer Alan R. , Huang Wenyu , Kuang Alan , Jimenez Maria , Lowe Lynn P. , Lowe William L. , Metzger Boyd E. , Nodzenski Michael , Reisetter Anna , Scholtens Denise , Talbot Octavious , Yim Paul , Dunger David , Thomas Alicia , Horlick Mary , Linder Barbara , Unalp-Arida Aynur , Grave Gilman 
Published: January 2019

OBJECTIVE
This study examined associations of maternal glycemia during pregnancy with childhood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.

RESEARCH DESIGN AND METHODS
HAPO was an observational international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-up Study included 4,832 children ages 10–14 years whose mothers had a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks of gestation. Of these, 4,160 children were evaluated for glucose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT.

RESULTS
Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, frequencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insulin sensitivity and disposition index decreased.

CONCLUSIONS
Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glucose and insulin resistance independent of maternal and childhood BMI and family history of diabetes.