Table 4.
Genotype frequencies and odds ratios for cases and controls,a by sex, for stratified neurodevelopmental outcomesb
| Gene | RS | Allele | Males | Females | p-Value for heterogeneity | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases | Controls | OR (95% Cl) | p-Value | Cases | Controls | OR (95% Cl) | p-Value | ||||||||||||
| m/M | MM | Mm | mm | MM | Mm | mm | MM | Mm | mm | MM | Mm | mm | |||||||
| Psychomotor delay | |||||||||||||||||||
| IL1β | 1143623 | G/C | 57.9 | 36.8 | 5.3 | 70.7 | 25.9 | 3.4 | 2.1 (0.8–5.4) | 0.14 | 70.6 | 20.6 | 8.8 | 51.4 | 42.9 | 5.7 | 0.6 (0.2–1.8) | 0.32 | 0.04 |
| IL6 | 2069840 | G/C | 59.3 | 33.9 | 6.8 | 49.1 | 36.8 | 14.0 | 0.5 (0.2–1.1) | 0.10 | 46.9 | 43.8 | 9.4 | 66.7 | 27.3 | 6.1 | 2.0 (0.7–5.5) | 0.20 | 0.05 |
| IL10 | 1800896 | C/T | 27.3 | 60.0 | 12.7 | 44.6 | 42.9 | 12.5 | 5.3 (1.6–17.6) | 0.007 | 51.5 | 24.2 | 24.2 | 35.3 | 41.2 | 23.5 | 0.6 (0.2–1.4) | 0.22 | 0.005 |
| AQP4 | 9951307 | G/A | 27.6 | 58.6 | 13.8 | 36.2 | 46.6 | 17.2 | 1.0 (0.5–2.1) | 0.91 | 21.9 | 62.5 | 15.6 | 43.8 | 50.0 | 6.3 | NA | 0.07 | 0.03 |
| Mental delay | |||||||||||||||||||
| IL6 | 1880243 | A/C | 65.3 | 25.0 | 9.7 | 65.8 | 31.5 | 2.7 | 1.0 (0.5–1.9) | 0.93 | 58.8 | 35.3 | 5.9 | 78.4 | 21.6 | 0 | 4.1 (0.9–18.7) | 0.07 | 0.02 |
| IL6 | 1800796 | C/G | 76.3 | 17.1 | 6.6 | 74.7 | 20.0 | 5.3 | 1.2 (0.6–2.4) | 0.62 | 77.8 | 22.2 | 0 | 67.7 | 23.5 | 8.8 | 0.3 (0.1–0.9) | 0.04 | 0.02 |
| IL6 | 2069840 | G/C | 58.1 | 31.1 | 10.8 | 53.5 | 35.2 | 11.3 | 0.7 (0.4–1.5) | 0.37 | 42.4 | 42.4 | 15.2 | 66.7 | 27.8 | 5.6 | 3.6 (1.1–12.1) | 0.04 | 0.02 |
| IL6R | 7549338 | C/G | 32.9 | 51.4 | 15.7 | 46.5 | 40.8 | 12.7 | 1.9 (1.0–3.7) | 0.05 | 41.9 | 41.9 | 16.1 | 29.4 | 47.1 | 23.5 | 0.6 (0.2–1.9) | 0.37 | 0.04 |
| IL6R | 7549250 | C/T | 22.9 | 57.1 | 20.0 | 48.4 | 34.4 | 17.2 | 1.7 (0.9–3.2) | 0.08 | 30.6 | 58.3 | 11.1 | 25.7 | 51.4 | 22.9 | 0.4 (0.2–1.2) | 0.09 | 0.01 |
| F7 | 6046 | A/G | 74.2 | 25.8 | 0 | 81.8 | 16.7 | 1.5 | 2.0 (0.7–5.4) | 0.20 | 96.4 | 0 | 3.6 | 69.0 | 27.6 | 3.5 | 0.1 (0.0–1.5) | 0.10 | 0.03 |
| TLR1 | 5743551 | T/C | 45.7 | 35.7 | 18.6 | 39.2 | 32.4 | 28.4 | 0.6 (0.3–1.2) | 0.18 | 29.7 | 48.6 | 21.6 | 54.3 | 28.6 | 17.1 | 2.6 (0.9–7.3) | 0.08 | 0.02 |
| Death/cerebral palsy | |||||||||||||||||||
| IL1β | 16944 | A/G | 34.9 | 34.9 | 30.2 | 37.8 | 50.0 | 12.2 | 1.9 (0.9–4.1) | 0.12 | 29.2 | 45.8 | 25.0 | 34.0 | 38.3 | 27.7 | 0.5 (0.2–1.2) | 0.13 | 0.01 |
| IL1β | 4848306 | A/G | 65.1 | 23.3 | 11.6 | 36.1 | 50.6 | 13.3 | 0.5 (0.2–1.3) | 0.15 | 52.0 | 36.0 | 12.0 | 54.2 | 37.5 | 8.3 | 1.7 (0.7–3.9) | 0.23 | 0.04 |
| IL6 | 2069840 | G/C | 67.6 | 24.3 | 8.1 | 51.3 | 36.3 | 12.5 | 0.9 (0.3–2.6) | 0.84 | 33.3 | 45.8 | 20.8 | 62.5 | 35.4 | 2.1 | 4.2 (1.3–13.4) | 0.02 | 0.01 |
| TNFα | 1800629 | A/G | 89.2 | 10.8 | 0 | 69.2 | 29.5 | 1.3 | 0.4 (0.1–1.9) | 0.24 | 52.4 | 47.6 | 0 | 66.7 | 31.0 | 2.4 | 10.4 (1.1–102.6) | 0.04 | 0.01 |
| MBL2 | 7096206 | G/C | 67.5 | 30.0 | 2.5 | 69.1 | 28.4 | 2.5 | 0.9 (0.3–2.6) | 0.79 | 79.2 | 20.8 | 0 | 65.9 | 27.3 | 6.8 | 0.2 (0.0–0.9) | 0.04 | 0.05 |
| F7 | 6046 | A/G | 82.4 | 17.6 | 0 | 80.3 | 18.4 | 1.3 | 0.3 (0.1–1.5) | 0.15 | 90.9 | 9.1 | 0 | 64.1 | 30.8 | 5.1 | 0.0 (0.0–0.6) | 0.03 | 0.02 |
| RAGE | 3134945 | A/C | 76.7 | 20.9 | 2.3 | 65.5 | 28.7 | 5.7 | 0.4 (0.1–1.5) | 0.19 | 47.8 | 52.2 | 66.0 | 30.0 | 4.0 | 7.6 (1.1–54.1) | 0.04 | 0.01 | |
Abbreviations: CI, confidence interval; OR, odds ratio; RS, reference sequence.
Cases are infants who died by the age of 1 year or developed CP, mental, or psychomotor delay by the age of 2 years. Controls were survivors with normal neurodevelopment, defined as Bayley MDI and PDI ≥85, and no diagnosis of CP, periventricular leukomalacia or grade III/IV intraventricular hemorrhage.
Additive genetic model used. All models adjusted for gestational age at birth, maternal education level, and exposure to magnesium sulfate (MgSO4). Maternal race/ethnicity was controlled through matching. Results reported for polymorphisms associated with composite adverse neurodevelopmental outcome at p < 0.05 for heterogeneity across strata. No loci were significantly different between males and females after correction for multiple comparisons.