All sites unadjusted treatment effects for ECD outcomes at 24 months of age
| ECD outcome | Pooled cohort (n=667) | Arm 1 (n=217) | Arm 2 (n=230) | Arm 3 (n=220) | Unadjusted pairwise arm comparisons | |
| INTER-NDA domain scores*, median (IQR) | ||||||
| Cognitive | 30.77 (23.10) | 30.77 (25.60) | 30.77 (20.50) | 36.59 (23.10) | H=1.65, p=0.44 η2<0.001 | |
| Language | 50.00 (41.70) | 47.22 (41.70) | 47.22 (38.90) | 51.52 (41.70) | H=2.82, p=0.24 η2<0.001 | |
| Fine motor | 11.11 (16.70) | 11.11 (16.70) | 11.11 (22.20) | 11.11 (16.70) | H=0.09, p=0.96 η2<0.001 | |
| Gross motor | 11.11 (22.20) | 11.11 (22.20) | 22.22 (22.20) | 22.22 (33.30) | H=0.54, p=0.76 η2<0.001 | |
| Positive behaviour | 90.00 (50.00) | 100.00 (40.00) | 100.00 (50.00) | 90.00 (50.00) | H=5.05, p=0.08 η2=0.004 | |
| Negative behaviour | 100.00 (25.00) | 100.00 (25.00) | 100.00 (25.00) | 100.00 (50.00) | H=3.44, p=0.18 η2=0.002 | |
| Risk of severe delay/problems†¶, n (%) | ||||||
| Cognitive | 246 (36.9) | 89 (41.0) | 82 (35.6) | 75 (34.1) | χ2=3.81, p=0.43 Cramer’s V=0.05 | |
| Language | 37 (5.6) | 17 (7.8) | 9 (3.9) | 11 (5.0) | χ2=3.95, p=0.41 Cramer’s V=0.06 | |
| Fine motor | 506 (75.9) | 164 (75.6) | 170 (73.9) | 172 (78.2) | χ2=3.98, p=0.41 Cramer’s V=0.06 | |
| Gross motor | 506 (75.9) | 166 (76.5) | 178 (77.4) | 162 (73.6) | χ2=4.11, p=0.39 Cramer’s V=0.06 | |
| Positive behaviour | 49 (7.4) | 15 (6.9) | 18 (7.8) | 16 (7.3) | χ2=6.33, p=0.18 Cramer’s V=0.07 | |
| Negative behaviour | 379 (56.8) | 136 (62.7) | 123 (53.5) | 120 (54.6) | χ2=5.92, p=0.21 Cramer’s V=0.07 | |
| Risk of any delay/problems‡**, n (%) | ||||||
| Cognitive | 444 (66.6) | 150 (69.1) | 156 (67.8) | 138 (62.7) | χ2=2.26, p=0.32 Cramer’s V=0.06 | |
| Language | 78 (11.7) | 30 (13.8) | 21 (9.1) | 27 (12.3) | χ2=2.49, p=0.29 Cramer’s V=0.06 | |
| Fine motor | 583 (87.4) | 191 (88.0) | 202 (87.8) | 190 (86.4) | χ2=0.33, p=0.85 Cramer’s V=0.02 | |
| Gross motor | 609 (91.3) | 195 (89.9) | 210 (91.3) | 204 (92.7) | χ2=1.13, p=0.56 Cramer’s V=0.04 | |
| Positive behaviour | 173 (25.9) | 47 (21.7) | 58 (25.2) | 68 (30.9) | χ2=4.96, p=0.08 Cramer’s V=0.09 | |
| Negative behaviour | 615 (92.2) | 202 (93.1) | 214 (93.0) | 199 (90.5) | χ2=1.40, p=0.50, Cramer’s V=0.05 | |
| Vision, median (IQR) | (n=613) | (n=206) | (n=205) | (n=202) | ||
| Visual acuity (logMar) | 0.40 (0.20) | 0.30 (0.20) | 0.40 (0.30) | 0.40 (0.10) | H=0.33, p=0.85 η2=0.002 | |
| Contrast sensitivity (%) | 3.00 (1.00) | 3.00 (1.50) | 3.00 (1.00) | 3.00 (1.00) | H=0.11, p=0.95 η2=0.003 | |
| Risk of low vision, n (%) | ||||||
| Visual acuity | 160 (24.0) | 53 (24.4) | 58 (25.2) | 49 (22.3) | χ2=0.70, p=0.71 Cramer’s V=0.03 | |
| Contrast sensitivity | 129 (19.3) | 46 (21.2) | 46 (20.0) | 37 (16.8) | χ2=1.54, p=0.46 Cramer’s V=0.05 | |
| Cortical auditory ERPs: peak amplitudes (in μV)§, median (IQR) | ||||||
| (n=123) | (n=39) | (n=39) | (n=45) | |||
| P1 | Frequent | 4.65 (4.36) | 4.63 (3.84) | 4.77 (4.68) | 4.05 (3.18) | F=0.39, p=0.67 η2=0.007 |
| Infrequent | 3.57 (2.27) | 3.29 (2.55) | 3.96 (2.31) | 3.56 (1.93) | F=0.89, p=0.41 η2=0.015 | |
| Novel | 3.74 (2.55) | 3.48 (3.07) | 3.78 (2.25) | 3.85 (2.30) | F=0.23, p=0.79 η2=0.004 | |
| N2 | Frequent | 4.30 (8.67) | 3.31 (3.24) | 3.19 (2.20) | 4.14 (3.53) | F=1.20, p=0.30 η2=0.02 |
| Infrequent | 2.81 (1.94) | 3.34 (2.00) | 2.39 (1.59) | 2.62 (2.01) | F=2.69, p=0.07 η2=0.04 | |
| Novel | 2.74 (1.98) | 2.48 (2.06) | 3.12 (1.30) | 2.64 (2.38) | F=1.10, p=0.34 η2=0.04 | |
| P3a | Frequent | 3.68 (3.28) | 3.52 (2.28) | 3.90 (3.21) | 3.09 (1.74) | F=1.14, p=0.32 η2=0.02 |
| Infrequent | 2.93 (1.58) | 2.65 (1.43) | 2.98 (1.64) | 3.14 (1.60) | F=1.06, p=0.35 η2=0.02 | |
| Novel | 2.82 (1.70) | 3.03 (1.81) | 2.64 (1.52) | 2.77 (1.78) | F=0.53, p=0.59 η2=0.009 | |
| Cortical auditory ERPs: latencies (in ms)§, median (IQR) | ||||||
| P1 | Frequent | 180.73 (37.92) | 183.42 (39.22) | 181.26 (36.18) | 176.23 (37.59) | F=0.40, p=0.67 η2=0.007 |
| Infrequent | 182.59 (34.01) | 181.35 (33.42) | 181.05 (32.70) | 185.27 (36.57) | F=0.20, p=0.82 η2=0.003 | |
| Novel | 190.16 (34.96) | 189.59 (35.13) | 181.97 (31.83) | 197.65 (36.87) | F=2.11, p=0.13 η2=0.034 | |
| N2 | Frequent | 294.29 (26.86) | 293.13 (30.03) | 291.14 (25.69) | 297.40 (24.98) | F=0.59, p=0.55 η2=0.01 |
| Infrequent | 297.78 (30.60) | 293.78 (33.91) | 304.27 (27.89) | 296.23 (29.62) | F=1.27, p=0.29 η2=0.02 | |
| Novel | 298.60 (32.33) | 293.89 (31.79) | 294.22 (33.51) | 306.90 (31.14) | F=2.25, p=0.11 η2=0.04 | |
| P3a | Frequent | 389.33 (32.07) | 389.86 (36.77) | 387.42 (29.82) | 390.45 (30.54) | F=0.09, p=0.91 η2=0.002 |
| Infrequent | 389.32 (34.14) | 396.31 (35.55) | 392.44 (33.87) | 380.08 (32.14) | F=2.64, p=0.08 η2=0.04 | |
| Novel | 387.57 (34.31) | 381.68 (34.26) | 394.94 (33.71) | 386.03 (34.81) | F=1.52, p=0.22 η2=0.03 | |
Arm 1: preconception intervention; arm 2: prenatal intervention; arm 3: no intervention.
*For all INTER-NDA outcomes, except negative behaviour, higher scores reflect better outcomes.
†For all INTER-NDA outcomes, except negative behaviour, high and any risk of delay are defined as domain scores ≤3rd and ≤10th centiles on the INTER-NDA standards, respectively. For negative behaviour, high and any risk of problems are defined as domain scores ≥97th and ≥90th centiles on the INTER-NDA standards, respectively.
‡For all INTER-NDA outcomes, except negative behaviour, mild-to-moderate risk of delay is defined as domain scores between the 3rd and 10th centiles on the INTER-NDA standards. For negative behaviour, mild-to-moderate risk of delay is defined as domain scores between the 90th and 97th centiles on the INTER-NDA standards.
§ERP values presented are averaged across the four temporal electrodes (T3–T6).
¶Comparisons made between arms for children with no delay versus mild-to-moderate delay versus severe delay.
**Comparisons made between arms for children with any delay versus no delay. η2=eta square.
ECD, early child development; ERP, evoked response potentials; INTER-NDA, INTERGROWTH-21st Neurodevelopment Assessment; logMar, logarithm of the minimum angle of resolution.