Table 4. Associations Between Severity of Neonatal Hypoglycemia and Neurocognitive Outcomes at Corrected Age 2 Yearsa.
| Variable | No./total (%) | RD/MD (95% CI) | RR (95% CI) | Adjusted RR/MD (95% CI)b | P valuec |
|---|---|---|---|---|---|
| Moderate or severe neurosensory impairmentd | .55 | ||||
| None | 20/704 (2.8) | 1 [Reference] | 1 [Reference] | 1 [Reference] | |
| Mild hypoglycemia | 16/381 (4.2) | 1.36 (−1.00 to 3.72) | 1.48 (0.77 to 2.82) | 1.42 (0.74 to 2.75) | .29 |
| Severe hypoglycemia | 4/106 (3.8) | 0.93 (−2.90 to 4.77) | 1.33 (0.46 to 3.82) | 1.51 (0.51 to 4.52) | .46 |
| Cerebral palsy | .41 | ||||
| None | 1/700 (0.1) | 1 [Reference] | 1 [Reference] | ||
| Mild hypoglycemia | 1/377 (0.3) | 0.12 (−0.47 to 0.71) | 1.86 (0.12 to 29.69) | NC | |
| Severe hypoglycemia | 1/104 (1.0) | 0.82 (−1.08 to 2.72) | 6.73 (0.42 to 107.23) | NC | |
| Developmental delaye | .11 | ||||
| None | 114/701 (16.3) | 1 [Reference] | 1 [Reference] | 1 [Reference] | |
| Mild hypoglycemia | 69/377 (18.3) | 2.04 (−2.73 to 6.81) | 1.13 (0.86 to 1.48) | 1.10 (0.83 to 1.45) | .51 |
| Severe hypoglycemia | 25/106 (23.6) | 7.32 (−1.22 to 15.87) | 1.45 (0.99 to 2.13) | 1.54 (1.05 to 2.26) | .03 |
| Cognitive delaye | .24 | ||||
| None | 42/703 (6.0) | 1 [Reference] | 1 [Reference] | 1 [Reference] | |
| Mild hypoglycemia | 24/380 (6.3) | 0.34 (−2.67 to 3.35) | 1.06 (0.65 to 1.72) | 1.07 (0.65 to 1.75) | .80 |
| Severe hypoglycemia | 11/106 (10.4) | 4.40 (−1.67 to 10.48) | 1.74 (0.92 to 3.27) | 1.78 (0.94 to 3.37) | .08 |
| Language delaye | .05 | ||||
| None | 104/702 (14.8) | 1 [Reference] | 1 [Reference] | 1 [Reference] | |
| Mild hypoglycemia | 61/380 (16.1) | 1.24 (−3.30 to 5.77) | 1.08 (0.81 to 1.45) | 1.06 (0.79 to 1.42) | .72 |
| Severe hypoglycemia | 24/106 (22.6) | 7.83 (−0.58 to 16.23) | 1.53 (1.03 to 2.27) | 1.65 (1.11 to 2.45) | .01 |
| Motor delaye | .13 | ||||
| None | 10/702 (1.4) | 1 [Reference] | 1 [Reference] | 1 [Reference] | |
| Mild hypoglycemia | 5/377 (1.3) | −0.10 (−1.55 to 1.35) | 0.93 (0.32 to 2.71) | 1.02 (0.34 to 3.04) | .98 |
| Severe hypoglycemia | 4/106 (3.8) | 2.35 (−1.39 to 6.09) | 2.65 (0.84 to 8.31) | 3.40 (1.03 to 11.21) | .04 |
| Bayley-III cognitive score, mean (SD) [total]e | .08 | ||||
| None | 99.0 (11.2) [703] | 1 [Reference] | NA | 1 [Reference] | |
| Mild hypoglycemia | 97.9 (10.7) [380] | −1.11 (−2.51 to 0.30) | NA | −1.39 (−2.79 to −0.00) | .05 |
| Severe hypoglycemia | 97.5 (12.8) [106] | −1.54 (−3.84 to 0.76) | NA | −1.62 (−3.97 to 0.73) | .18 |
| Bayley-III language score, mean (SD) [total]e | .49 | ||||
| None | 98.6 (15.0) [702] | 1 [Reference] | NA | 1 [Reference] | |
| Mild hypoglycemia | 98.6 (15.8) [380] | −0.02 (−1.94 to 1.90) | NA | −0.13 (−2.05 to 1.79) | .90 |
| Severe hypoglycemia | 97.2 (15.7) [106] | −1.45 (−4.59 to 1.68) | NA | −2.06 (−5.17 to 1.04) | .19 |
| Bayley-III motor score, mean (SD) [total No.]e | .003 | ||||
| None | 104.8 (10.8) [702] | 1 [Reference] | NA | 1 [Reference] | |
| Mild hypoglycemia | 103.3 (9.9) [377] | −1.49 (−2.81 to −0.16) | NA | −1.69 (−3.04 to −0.34) | .01 |
| Severe hypoglycemia | 101.8 (11.3) [106] | −3.00 (−5.16 to −0.84) | NA | −3.39 (−5.67 to −1.11) | .004 |
| Poor executive functionf | .41 | ||||
| None | 36/701 (5.1) | 1 [Reference] | 1 [Reference] | 1 [Reference] | |
| Mild hypoglycemia | 24/377 (6.4) | 1.23 (−1.73 to 4.19) | 1.24 (0.75 to 2.05) | 1.24 (0.74 to 2.06) | .42 |
| Severe hypoglycemia | 9/106 (8.5) | 3.36 (−2.21 to 8.92) | 1.65 (0.82 to 3.34) | 1.56 (0.75 to 3.24) | .23 |
| Executive function total score, mean (SD) [total No.]g | .19 | ||||
| None | 10.6 (4.4) [701] | 1 [Reference] | NA | 1 [Reference] | |
| Mild hypoglycemia | 10.5 (4.5) [377] | −0.07 (−0.63 to 0.48) | NA | −0.01 (−0.54 to 0.57) | .96 |
| Severe hypoglycemia | 9.5 (4.5) [106] | −1.11 (−2.01 to −0.20) | NA | −0.82 (−1.73 to 0.10) | .08 |
Abbreviations: Bayley-III, Bayley Scales of Infant and Toddler Development, Third Edition; MD, mean difference; NA. not applicable; NC, not calculated owing to small numbers; RD, risk difference; RR, risk ratio.
The severity of hypoglycemia was defined as none (all blood glucose concentrations ≥47 mg/dL), mild (≥1 episode of ≥36 and <47 mg/dL), and severe (≥1 episode of <36 mg/dL) (to convert glucose to millimoles per liter, multiply by 0.0555).
Adjusted for study site, primary reason for risk of hypoglycemia, socioeconomic decile at birth, and multiple births.
P value reported is for the overall association between severity of hypoglycemia and outcome, none vs mild, and/or none vs severe.
Defined as any of the following: blindness, hearing impairment requiring aids, moderate or severe cerebral palsy (not walking yet or permanently nonambulant), or moderate or severe developmental delay.
One child in the hypoglycemia group was assigned a score of 49 for the Bayley-III cognitive, language, and motor scales because the child was unable to finish the assessment owing to severe delay. Language, cognitive, and motor scales, mean (100), SD (15), higher scores indicate better performance.
Poor executive function defined as an executive function total score more than 1.5 SD below the mean.
Total score range 0 to 24 points; higher scores indicate better performance. eTable 2 in the Supplement presents the executive function component results.