Table 2.
Regression analysis of offspring outcomes between control (no analgesic) and groups exposed to at least one analgesic, only paracetamol, and at least one from ibuprofen (Ibu), aspirin (Asp), naproxen (Napr)
| Outcomes | No analgesic (n=107 143) n (%) |
At least one analgesic (n=43 998) n (%) |
Crude OR (95% CI) |
Adjusted OR (95% CI) |
Paracetamol only (n=24 099) n (%) |
Crude OR (95% CI) |
Adjusted OR (95% CI) |
Ibu/Asp/Napr (n=762) n (%) |
Crude OR (95% CI) |
Adjusted OR (95% CI) |
| Gestation at delivery (weeks) | ||||||||||
| −37 | 100 879 (94.2) | 39 838 (90.5) | 1.00 | 1.00 | 21 589 (89.6) | 1.00 | 1.00 | 697 (91.5) | 1.00 | 1.00 |
| <37 | 6264 (5.8) | 4160 (9.5) | 1.68 (1.61 to 1.75) | 1.50 (1.43 to 1.58)* | 2510 (10.4) | 1.87 (1.78 to 1.97) | 1.56 (1.48 to 1.65)* | 65 (8.5) | 1.50 (1.16 to 1.94) | 1.42 (1.08 to 1.86)* |
| Pregnancy outcome | ||||||||||
| Live birth | 105 949 (98.9) | 43 407 (98.7) | 1.00 | 1.00 | 23 704 (98.4) | 1.00 | 1.00 | 747 (98.0) | 1.00 | 1.00 |
| Stillbirth | 803 (0.7) | 405 (0.9) | 1.23 (1.09 to 1.39) | 1.33 (1.15 to 1.54)* | 275 (1.1) | 1.53 (1.33 to 1.76) | 1.52 (1.30 to 1.77)* | 13 (1.7) | 2.30 (1.32 to 3.99) | 2.34 (1.29 to 4.25)* |
| Neonatal death | 373 (0.3) | 182 (0.4) | 1.19 (0.99 to 1.42) | 1.56 (1.27 to 1.93)* | 117 (0.5) | 1.40 (1.14 to 1.73) | 1.56 (1.24 to 1.96)* | 2 (0.3) | 0.76 (0.19 to 3.06) | 0.93 (0.23 to 3.74)* |
| Missing | 18 (<0.1) | 4 (<0.1) | n/a | n/a | 3 (<0.1) | n/a | n/a | 0 (0.0) | n/a | n/a |
| Weight of baby (g) | ||||||||||
| NBW | 87 966 (82.1) | 34 555 (78.6) | 1.00 | 1.00 | 19 163 (79.5) | 1.00 | 1.00 | 605 (79.5) | 1.00 | 1.00 |
| LBW | 5910 (5.5) | 3571 (8.1) | 1.54 (1.47 to 1.61) | 1.28 (1.20 to 1.37)† | 2213 (9.2) | 1.72 (1.63 to 1.81) | 1.60 (1.51 to 1.69)† | 59 (7.7) | 1.45 (1.11 to 1.90) | 1.29 (0.91 to 1.83)† |
| HBW | 13 233 (12.4) | 5863 (13.3) | 1.13 (1.09 to 1.17) | 1.09 (1.05 to 1.13)† | 2720 (11.3) | 0.94 (0.90 to 0.99) | 0.98 (0.93 to 1.02)† | 97 (12.7) | 1.07 (0.86 to 1.32) | 0.99 (0.80 to 1.24)† |
| Missing | 34 (<0.1) | 9 (<0.1) | n/a | n/a | 3 (<0.1) | n/a | n/a | 1 (0.1) | n/a | n/a |
| Standardised birthweight score | ||||||||||
| Mean (SD) | 0.001 (0.003) | −0.002 (0.065) | 0.03 (0.02 to 0.04) | 0.046 (0.032 to 0.059) ‡ | 0.001 (0.991) | −0.04 (−0.058 to -0.029) | −0.014 (−0.029 to 0.001) ‡ | 0.046 (0.038) | 0.045 (−0.029 to 0.119) | 0.049 (−0.025 to 0.123) ‡ |
| Admitted to neonatal unit | ||||||||||
| No | 62 378 (58.2) | 32 391 (73.6) | 1.00 | 1.00 | 16 342 (67.8) | 1.00 | 1.00 | 480 (63.0) | 1.00 | 1.00 |
| Yes | 11 011 (10.3) | 7448 (16.9) | 1.30 (1.26 to 1.35) | 1.57 (1.51 to 1.64)† | 3956 (16.4) | 1.37 (1.32 to 1.43) | 1.45 (1.38 to 1.53)† | 117 (15.4) | 1.38 (1.13 to 1.69) | 1.54 (1.22 to 1.94)† |
| Missing | 33 754 (31.5) | 4159 (9.5) | n/a | n/a | 3801 (15.8) | n/a | n/a | 762 (21.7) | n/a | n/a |
| APGAR score at 1 min | ||||||||||
| Normal | 92 217 (86.1) | 38 224 (86.9) | 1.00 | 1.00 | 20 593 (85.5) | 1.00 | 1.00 | 659 (86.5) | 1.00 | 1.00 |
| <7 | 14 335 (13.4) | 5674 (12.9) | 0.96 (0.92 to 0.99) | 1.18 (1.13 to 1.23)§ | 3437 (14.3) | 1.07 (1.03 to 1.12) | 1.23 (1.18 to 1.28)§ | 101 (13.3) | 0.99 (0.80 to 1.22) | 1.07 (0.86 to 1.32)§ |
| Missing | 591 (0.6) | 100 (0.2) | n/a | 69 (0.3) | n/a | n/a | 2 (0.3) | n/a | n/a | |
| APGAR score at 5 min | ||||||||||
| Normal | 104 292 (97.3) | 42 730 (97.1) | 1.00 | 1.00 | 23 334 (96.8) | 1.00 | 1.00 | 738 (96.9) | 1.00 | 1.00 |
| <7 | 2216 (2.1) | 1163 (2.6) | 1.28 (1.19 to 1.38) | 1.48 (1.35 to 1.62)§ | 690 (2.9) | 1.39 (1.28 to 1.52) | 1.53 (1.40 to 1.68)§ | 21 (2.8) | 1.34 (0.87 to 2.07) | 1.52 (0.97 to 2.36)§ |
| Missing | 635 (0.6) | 105 (0.2) | n/a | n/a | 75 (0.3) | n/a | n/a | 3 (0.4) | n/a | n/a |
| Cryptorchidism (only males included) | ||||||||||
| No | 54 509 (99.3) | 22 616 (99.0) | 1.00 | 1.00 | 12 247 (99.1) | 1.00 | 1.00 | 394 (99.4) | 1.00 | 1.00 |
| Yes | 357 (0.7) | 236 (1.0) | 1.59 (1.35 to 1.88) | 0.92 (0.77 to 1.11)† | 107 (0.9) | 1.33 (1.07 to 1.66) | 0.87 (0.69 to 1.09)† | 1 (0.3) | 0.39 (0.05 to 2.77) | 0.28 (0.04 to 1.98)† |
| Neural tube defects | ||||||||||
| No | 107 093 (99.9) | 43 928 (99.8) | 1.00 | 1.00 | 24 077 (99.9) | 1.00 | 1.00 | 762 (100) | 1.00 | 1.00 |
| Yes | 50 (0.1) | 70 (0.2) | 3.41 (2.37 to 4.91) | 1.64 (1.08 to 2.47)† | 22 (0.1) | 1.96 (1.19 to 3.23) | 1.21 (0.71 to 2.06)† | 0 (0.0) | n/a | n/a |
| Amniotic band defects | ||||||||||
| No | 107 053 (99.9) | 43 936 (99.9) | 1.00 | 1.00 | 24 070 (99.9) | 1.00 | 1.00 | 760 (99.7) | 1.00 | 1.00 |
| Yes | 90 (0.1) | 62 (0.1) | 1.68 (1.21 to 2.32) | 1.02 (0.71 to 1.47)† | 29 (0.1) | 1.43 (0.94 to 2.18) | 0.98 (0.63 to 1.52)† | 2 (0.3) | 3.13 (0.77 to 12.73) | 2.29 (0.56 to 9.37)† |
| Hypospadias (only males included) | ||||||||||
| No | 54 607 (99.5) | 22 600 (98.9) | 1.00 | 1.00 | 12 258 (99.2) | 1.00 | 1.00 | 390 (98.7) | 1.00 | 1.00 |
| Yes | 259 (0.3) | 252 (1.1) | 2.35 (1.98 to 2.80) | 1.27 (1.05 to 1.54)† | 96 (0.8) | 1.65 (1.31 to 2.09) | 1.07 (0.84 to 1.37)† | 5 (1.3) | 2.70 (1.11 to 6.59) | 1.91 (0.78 to 4.68)† |
| Gastroschisis | ||||||||||
| No | 107 120 (99.9) | 43 979 (99.9) | 1.00 | 1.00 | 24 089 (99.9) | 1.00 | 1.00 | 762 (100) | 1.00 | 1.00 |
| Yes | 23 (0.1) | 19 (0.1) | 2.01 (1.10 to 3.70) | 1.10 (0.56 to 2.20)† | 10 (0.1) | 1.93 (0.92 to 4.06) | 0.99 (0.45 to 2.21)† | 0 (0.0) | n/a | n/a |
| At least one outcome¶ | ||||||||||
| No | 106 367 (99.3%) | 43 363 (98.6%) | 1.00 | 1.00 | 23 835 (98.9%) | 1.00 | 1.00 | 754 (99.0%) | 1.00 | 1.00 |
| Yes | 776 (0.7%) | 635 (1.4%) | 2.01 (1.81 to 2.23) | 1.12 (0.99 to 1.26)† | 264 (1.1%) | 1.52 (1.32 to 1.75) | 0.97 (0.84 to 1.13)† | 8 (1.0%) | 1.45 (0.72 to 2.93) | 1.11 (0.55 to 2.23)† |
Bold values show a significant OR (95% CI) as reported in the table.
*Adjusted for year of delivery, maternal age at delivery, SIMD, first gestational booking, maternal hypertensive disorders, maternal antepartum haemorrhage.
†Adjusted for year of delivery, maternal age at delivery, SIMD, first gestational booking, gestation at delivery.
‡Adjusted for year of delivery, maternal age at delivery, SIMD, first gestational booking.
§Adjusted for year of delivery, maternal age at delivery, SIMD, first gestational booking, type of delivery.
¶Including cryptorchidism, neural tube defects, amniotic band defects, hypospadias, gastroschisis.
n, number of pregnancies; n/a, not applicable; SIMD, Scottish Index of Multiple Deprivation.