Table 2.
Neurodevelopmental outcome at five years according to exposure and duration of exposure to opioids with/without midazolam.
| Unexposed (n = 1952), % | Exposed ≤7 days (n = 762), % | Exposed >7 days (n = 403), % | p value | Model 1: aOR or adjusted mean difference (95% CI), vs Unexposeda |
Model 2: aOR or adjusted mean difference (95% CI), vs Unexposeda |
|||
|---|---|---|---|---|---|---|---|---|
| Exposed ≤7 days | Exposed >7 days | Exposed ≤7 days | Exposed >7 days | |||||
| Neurodevelopmental disabilitiesb | ||||||||
| None | 43.8 | 40.6 | 26.2 | <0.001 | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Mild | 38.4 | 40.6 | 42.1 | 1.07 (0.84–1.37) | 1.47 (1.02–2.12) | 1.07 (0.84–1.37) | 1.37 (0.94–2.01) | |
| Moderate or Severe | 17.8 | 18.9 | 31.7 | 1.03 (0.76–1.41) | 2.07 (1.32–3.26) | 0.98 (0.71–1.34) | 1.43 (0.88–2.32) | |
| Cerebral palsy | 5.3 | 6.3 | 11.4 | <0.001 | 0.99 (0.66–1.49) | 1.45 (0.91–2.31) | 0.85 (0.54–1.35) | 0.85 (0.50–1.45) |
| Full scale intelligence quotient (FSIQ) | ||||||||
| mean (SD) | 94.4 (15.3) | 94.0 (15.9) | 87.6 (16.6) | <0.001 | 0.10 (−1.5 to 1.7) | −4.1 (−6.6 to −1.7) | 0.32 (−1.3 to 1.9) | −2.3 (−4.9 to 0.16) |
| < −2 SDc | 15.0 | 15.3 | 27.2 | <0.001 | 0.95 (0.71–1.27) | 1.58 (1.05–2.38) | 0.90 (0.67–1.21) | 1.14 (0.72–1.80) |
| Developmental Coordination Disorders, MABC-2 scored | ||||||||
| mean (SD) | 9.5 (3.8) | 9.4 (3.8) | 8.4 (3.7) | 0.007 | −0.01 (−0.40 to 0.38) | −0.53 (−1.2 to 0.12) | 0.02 (−0.38 to 0.41) | −0.33 (−0.99 to 0.32) |
| ≤5th percentilec | 14.3 | 14.5 | 23.3 | 0.1 | 0.88 (0.61–1.28) | 1.36 (0.77–2.38) | 0.87 (0.59–1.29) | 1.2 (0.68–2.13) |
| Behavioural difficulties, Total SDQ score | ||||||||
| mean (SD) | 10.6 (5.9) | 11.0 (6.1) | 11.7 (5.9) | <0.001 | 0.31 (−0.25 to 0.86) | 0.84 (−0.04 to 1.7) | 0.28 (−0.27 to 0.84) | 0.52 (−0.42 to 1.5) |
| ≥90th percentilec | 10.6 | 13.3 | 13.3 | 0.18 | 1.28 (0.93–1.75) | 1.26 (0.80–1.99) | 1.27 (0.93–1.75) | 1.12 (0.69–1.81) |
| Visual disability, moderate or severe disabilities | 1.0 | 1.0 | 2.0 | 0.006 | 1.11 (0.35–3.50) | 2.27 (0.54–9.64) | 1.07 (0.33–3.44) | 2.08 (0.46–9.30) |
| Hearing disability, moderate or severe disabilities | 0.8 | 1.4 | 2.3 | 0.1 | 1.49 (0.54–4.10) | 2.59 (0.69–9.76) | 1.39 (0.52–3.73) | 1.29 (0.31–5.40) |
Results after multiple imputation.
Percentages are weighted to consider the differences in survey design between gestational age groups.
aOR = adjusted odd ratios; CI = confidence interval; SD = Standard Deviation; GMFCS = Gross Motor Function Classification System; dB = decibel; FSIQ = Full scale intelligence quotient; MABC-2 = Movement Assessment Battery for Children- Second Edition; SDQ = Strengths and difficulties questionnaire; GA = Gestational Age.
Model 1: adjusted for gestational age in week, maternal age at birth, mother birth in France, parents’ socio-economic status, cause of preterm birth, antenatal corticosteroids, magnesium sulphate administration, multiple pregnancy, sex, small-for-GA, Apgar at 5 min < 7, birth in type 3 and neonatal unit volume. Model 2 is model 1 variables and severe neonatal morbidities (late onset sepsis, severe cerebral lesion, severe bronchopulmonary dysplasia, necrotizing enterocolitis, severe retinopathy of prematurity).
Severe = cerebral palsy gross motor function classification system (GMFCS) level 4/5, and/or bilateral binocular visual acuity <1/10, and/or uni or bilateral hearing loss >70 dB, and/or FSIQ < −3 SD; Moderate = cerebral palsy GMFCS level 2/3, and/or 3.2/10 < bilateral binocular visual acuity ≥1/10, and/or uni or bilateral hearing loss 40–70 dB and/or FSIQ between −3 and −2 SD; Mild = cerebral palsy GMFCS level 1, and/or 5/10 < uni or bilateral binocular visual acuity ≥3.2/10, and/or uni or bilateral hearing loss <40 db, and/or FSIQ between −2 and −1 SD, and/or total MABC-2 score ≤ 5th percentile, and/or behavioural difficulties according to SDQ score ≥90th percentile. Cut-off of the distribution related to a reference group born at term.1,19
Among children without cerebral palsy, severe or moderate sensory disabilities, and with full-scale intelligence quotient upper or equal than 2 standard deviations.