Table. Risk of ASD in Offspring Associated With Maternal HbA1c Levels in Early Pregnancya.
| HbA1c | ASD Cases/Total Children, No. (%) | Unadjusted Hazard Ratios (95% CI) | P Value | Adjusted Hazard Ratios (95% CI)b | P Value |
|---|---|---|---|---|---|
| As a continuous variable (per 1% increase) | 1.23 (1.08-1.41) | .002 | 1.12 (0.96-1.31) | .15 | |
| As a categorical variablec | |||||
| <5.7% | 574/30 419 (1.89) | 1 [Reference] | 1 [Reference] | ||
| 5.7%-5.9% | 101/4172 (2.42) | 1.24 (1.01-1.54) | .04 | 1.08 (0.87-1.35) | .46 |
| 6.0%-6.5% | 17/871 (1.95) | 0.98 (0.61-1.59) | .94 | 0.79 (0.48-1.28) | .33 |
| >6.5% | 15/357 (4.20) | 2.17 (1.30-3.62) | .003 | 1.79 (1.06-3.00) | .03 |
Abbreviations: ASD, autism spectrum disorder (includes autistic disorders, Asperger syndrome, or pervasive developmental disorder not otherwise specified); GD, gestational diabetes; HbA1c, hemoglobin A1c; T1D, preexisting type 1 diabetes; T2D, preexisting type 2 diabetes.
The median gestational age at HbA1c testing was 9.0 weeks (interquartile range, 6.7-11.4 weeks); 83% of the testing was in the first trimester. Potential confounders assessed included maternal age at delivery, prepregnancy body mass index, parity, education, self-reported race/ethnicity; gestational age at HbA1c testing; presence of comorbidity (diagnosis of heart, lung, kidney, or liver disease or cancer) prior to pregnancy; presence of anemia or hemoglobinopathies, smoking, preeclampsia/eclampsia, depression, use of selective serotonin reuptake inhibitors during pregnancy; and child’s sex. None of them changed the model estimates by more than 10% except for maternal prepregnancy body mass index and race/ethnicity.
Estimated by Cox regression models adjusted for maternal race/ethnicity and prepregnancy body mass index (calculated as weight in kilograms divided by height in meters squared).
Distribution of diabetes status: overall: 0.4% T1D, 5.7% T2D, 9.3% GD, and 84.6% no diabetes; for HbA1c greater than 6.5%: 19.9% T1D, 70.6% T2D, 8.1% GD, and 1.4% no diabetes; for HbA1c between 6.0% and 6.5%: 2.6% T1D, 37.3% T2D, 31.3% GD, and 28.7% no diabetes; for HbA1c between 5.7% and 5.9%: 0.3% T1D, 14.2% T2D, 17.4% GD, and 68.1% no diabetes; and for HbA1c less than 5.7%: 0.1% T1D, 2.8% T2D, 7.6% GD, and 89.5% no diabetes.