Table 3.
Neurodevelopmental outcome at five years according to exposure and duration of exposure, by drug.
| Unexposed, % | Exposed ≤7 days, % | Exposed >7 days, % | 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 | |||||
| Opioids | n = 1952 | n = 453 | n = 113 | |||||
| Neurodevelopmental disabilitiesb | ||||||||
| None | 43.8 | 42.5 | 25.8 | 0.006 | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Mild | 38.4 | 39.3 | 41.9 | 0.99 (0.74–1.32) | 1.45 (0.72–2.93) | 0.98 (0.73–1.30) | 1.39 (0.71–2.72) | |
| Moderate or Severe | 17.8 | 18.1 | 32.3 | 0.97 (0.62–1.29) | 1.91 (0.86–4.38) | 0.91 (0.61–1.34) | 1.40 (0.62–3.15) | |
| Cerebral palsy | 5.3 | 6.0 | 10.0 | 0.28 | 0.92 (0.58–1.46) | 1.12 (0.48–2.63) | 0.85 (0.50–1.45) | 0.73 (0.29–1.83) |
| Full scale intelligence quotient (FSIQ) | ||||||||
| Mean (SD) | 94.4 (15.3) | 94.3 (15.8) | 88.3 (16.0) | 0.016 | 0.4 (−1.5 to 2.2) | −3.0 (−7.1 to 1.1) | 0.4 (−1.5 to 2.2) | −1.4 (−5.3 to 2.5) |
| <−2 SDc | 15.0 | 14.8 | 27.5 | 0.014 | 0.92 (0.63–1.34) | 1.52 (0.82–2.81) | 0.91 (0.62–1.33) | 1.07 (0.55–2.08) |
| Developmental coordination disorders, MABC-2 scored | ||||||||
| Mean (SD) | 9.5 (3.8) | 9.5 (3.8) | 8.4 (3.8) | 0.17 | 0.1 (−0.4 to 0.6) | −0.5 (−1.5 to 0.6) | 0.1 (−0.4 to 0.6) | −0.2 (−1.3 to 0.8) |
| ≤5th percentilec | 14.3 | 13.0 | 25.4 | 0.089 | 0.69 (0.36–1.29) | 1.45 (0.67–3.16) | 0.69 (0.37–1.30) | 1.31 (0.58–2.97) |
| Behavioural difficulties, total SDQ score | ||||||||
| mean (SD) | 10.6 (5.9) | 10.8 (6.1) | 11.6 (6) | 0.26 | 0.0 (−0.6 to 0.7) | 0.4 (−1.2 to 2.1) | 0.0 (−0.6 to 0.7) | 0.2 (−1.4 to 1.8) |
| ≥90th percentilec | 10.6 | 12.6 | 12.8 | 0.48 | 1.22 (0.86–1.73) | 1.07 (0.52–2.18) | 1.22 (0.86–1.73) | 0.97 (0.47–2.00) |
| Opioids and midazolam | n = 1952 | n = 218 | n = 278 | |||||
| Neurodevelopmental disabilitiesb | ||||||||
| None | 43.8 | 35.3 | 26.9 | <0.001 | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Mild | 38.4 | 43.4 | 41.2 | 1.26 (0.86–1.85) | 1.39 (0.96–2.02) | 1.25 (0.85–1.83) | 1.27 (0.83–1.94) | |
| Moderate or Severe | 17.8 | 21.3 | 31.9 | 1.19 (0.74–1.92) | 2.10 (1.29–3.44) | 1.04 (0.63–1.72) | 1.36 (0.79–2.34) | |
| Cerebral palsy | 5.3 | 7.7 | 12 | <0.001 | 1.13 (0.60–2.16) | 1.50 (0.89–2.51) | 0.88 (0.44–1.73) | 0.80 (0.43–1.51) |
| Full scale intelligence quotient (FSIQ) | ||||||||
| Mean (SD) | 94.4 (15.3) | 92.8 (16.2) | 87.5 (16.9) | <0.001 | −0.01 (−2.6 to 2.6) | −4.5 (−7.2 to −1.7) | 0.53 (−2.1 to 3.1) | −2.4 (−5.4 to 0.51) |
| <−2 SDc | 15.0 | 17.1 | 27.4 | <0.001 | 0.94 (0.59–1.51) | 1.67 (1.04–2.69) | 0.84 (0.52–1.37) | 1.17 (0.68–2.02) |
| Developmental coordination disorders, MABC-2 scored | ||||||||
| Mean (SD) | 9.5 (3.8) | 9.0 (3.9) | 8.4 (3.6) | 0.008 | −0.24 (−0.89 to 0.42) | −0.46 (−1.2 to 0.30) | −0.16 (−0.83 to 0.50) | −0.19 (−0.96 to 0.58) |
| ≤5th percentilec | 14.4 | 18.6 | 22.0 | 0.11 | 1.26 (0.72–2.20) | 1.18 (0.61–2.28) | 1.20 (0.68–2.11) | 0.97 (0.48–1.98) |
| Behavioural difficulties, Total SDQ score | ||||||||
| Mean (SD) | 10.6 (5.9) | 11.6 (6.1) | 11.9 (5.8) | 0.002 | 0.70 (−0.23 to 1.6) | 1.3 (0.32–2.2) | 0.68 (−0.26 to 1.6) | 1.0 (0.01–2.1) |
| ≥90th percentilec | 10.6 | 14.8 | 13.9 | 0.15 | 1.36 (0.82–2.24) | 1.34 (0.80–2.24) | 1.35 (0.81–2.24) | 1.25 (0.71–2.19) |
Results after multiple imputation.
Percentages are weighted to consider the differences in survey design between gestational age groups.
aOR = adjusted odds 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.