Table 3. Associations Between Neonatal Hypoglycemia and Neurocognitive Outcomes at Corrected Age 2 Years.
| Secondary outcome | No./total No. (%) | RD/MD (95% CI) | RR (95% CI) | Adjusted RR/MD (95% CI)a | P valueb | |
|---|---|---|---|---|---|---|
| Hypoglycemia group (n = 490)c | Normoglycemia group (n = 704)c | |||||
| Moderate or severe neurosensory impairmentd | 20/487 (4.1) | 20/704 (2.8) | 1.27 (−0.88 to 3.42) | 1.45 (0.79 to 2.66) | 1.41 (0.76 to 2.62) | .28 |
| Cerebral palsy | 2/481 (0.4) | 1/700 (0.1) | 0.27 (−0.37 to 0.91) | NC | NC | |
| None | 479/481 (99.6) | 699/700 (99.9) | −0.27 (−0.91 to 0.37) | 1 [Reference] | 1 [Reference] | |
| Mild | 0/481 | 1/700 (0.1) | −0.14 (NE) | NE | NE | |
| Moderate or severe | 2/481 (0.4) | 0/700 | 0.42 (NE) | NE | NE | |
| Developmental delaye | 94/483 (19.5) | 114/701 (16.3) | 3.20 (−1.27 to 7.67) | 1.20 (0.93 to 1.53) | 1.18 (0.92 to 1.51) | .19 |
| None | 389/483 (80.5) | 587/701 (83.7) | −3.20 (−7.67 to 1.27) | 1 [Reference] | 1 [Reference] | |
| Mild | 79/483 (16.4) | 94/701 (13.4) | 2.95 (−1.21 to 7.10) | 1.22 (0.93 to 1.61) | 1.21 (0.92 to 1.59) | .18 |
| Moderate or severe | 15/483 (3.1) | 20/701 (2.9) | 0.25 (−1.73 to 2.23) | 1.13 (0.58 to 2.18) | 1.11 (0.57 to 2.17) | .76 |
| Cognitive delaye | 35/486 (7.2) | 42/703 (6.0) | 1.16 (−1.72 to 4.03) | 1.21 (0.78 to 1.86) | 1.22 (0.79 to 1.89) | .37 |
| None | 451/486 (92.8) | 661/703 (94.0) | −1.23 (−4.12 to 1.67) | 1 [Reference] | 1 [Reference] | |
| Mild | 31/486 (6.4) | 36/703 (5.1) | 1.26 (−1.46 to 3.98) | 1.25 (0.78 to 1.99) | 1.28 (0.80 to 2.06) | .30 |
| Moderate or severe | 4/486 (0.8) | 6/703 (0.9) | −0.03 (−1.08 to 1.02) | 0.98 (0.28 to 3.45) | 0.82 (0.23 to 2.85) | .76 |
| Language delaye | 85/486 (17.5) | 104/702 (14.8) | 2.68 (−1.61 to 6.96) | 1.18 (0.91 to 1.53) | 1.16 (0.89 to 1.52) | .26 |
| None | 401/486 (82.5) | 598/702 (85.2) | −2.68 (−6.96 to 1.61) | 1 [Reference] | 1 [Reference] | |
| Mild | 71/486 (14.6) | 87/702 (12.4) | 2.22 (−1.76 to 6.20) | 1.18 (0.89 to 1.58) | 1.17 (0.87 to 1.57) | .29 |
| Moderate or severe | 14/486 (2.9) | 17/702 (2.4) | 0.46 (−1.42 to 2.33) | 1.22 (0.61 to 2.45) | 1.18 (0.58 to 2.40) | .64 |
| Motor delaye | 9/483 (1.9) | 10/702 (1.4) | 0.44 (−1.05 to 1.93) | 1.31 (0.54 to 3.20) | 1.38 (0.56 to 3.42) | .48 |
| None | 474/483 (98.1) | 692/702 (98.6) | −0.44 (−1.93 to 1.05) | 1 [Reference] | 1 [Reference] | |
| Mild | 8/483 (1.7) | 7/702 (1.0) | 0.66 (−0.70 to 2.02) | 1.66 (0.60 to 4.54) | 1.77 (0.63 to 4.96) | .28 |
| Moderate or severe | 1/483 (0.2) | 3/702 (0.4) | −0.22 (−0.85 to 0.41) | 0.49 (0.05 to 4.69) | 0.53 (0.05 to 5.20) | .58 |
| Bayley-III total scores, mean (SD) [total No.]e | ||||||
| Cognitive score | 97.8 (11.2) [486] | 99.0 (11.2) [703] | −1.20 (−2.50 to 0.10) | NA | −1.48 (−2.79 to −0.18) | .03 |
| Language score | 98.3 (15.8) [486] | 98.6 (15.0) [702] | −0.33 (−2.11 to 1.44) | NA | −0.51 (−2.29 to 1.28) | .58 |
| Motor score | 103.0 (10.3) [483] | 104.8 (10.8) [702] | −1.82 (−3.05 to −0.59) | NA | −2.05 (−3.30 to −0.79) | .001 |
| Poor executive functionf | 33/483 (6.8) | 36/701 (5.1) | 1.70 (−1.09 to 4.48) | 1.33 (0.84 to 2.10) | 1.31 (0.82 to 2.10) | .25 |
| Executive function total score, mean (SD) [total No.]g | 10.3 (4.5) [483] | 10.6 (4.4) [701] | −0.30 (−0.82 to 0.22) | NA | −0.19 (−0.70 to 0.33) | .48 |
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; NE, not estimable; RD, risk difference; RR, risk ratio.
Adjusted for study site, primary reason for risk of hypoglycemia, socioeconomic decile at birth, and multiple births.
First P value reported in the outcome row is for the overall association between severity of hypoglycemia and outcome. The P values below in mild and severe rows are for the comparison between none vs mild or none vs severe.
An episode of hypoglycemia was defined as 1 or more episodes of consecutive blood glucose concentrations less than 47 mg/dL (to convert glucose to millimoles per liter, multiply by 0.0555).
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 due to severe delay. Language, cognitive, and motor scales, mean (100), SD (15), and higher scores indicate better performance.
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.