Table 3.
Risk difference (RD) of maternal and neonatal outcomes in the ADHD medication-exposed group versus the reference group
| Study | None exposure (A) | Exposure during pregnancy (B) | Alternative comparison groups (C) | RD (B minus A) | RD (C minus A) | ||||
|---|---|---|---|---|---|---|---|---|---|
| N | Number with outcome(n,%) | N | Number with outcome(n,%) | N | Number with outcome(n,%) | ||||
| Pregnancy complications | |||||||||
| Preeclampsia | Cohen et al, 2017 [47] | 1461493 | 54467(3.73%) | 4846 | 256(5.28%) | 453 | 22(4.86%)a | 1.55% | 1.13% |
| Poulton et al, 2018 [53] | 25,249 | 1509(5.98%) | 175 | 13(7.43%) | 4881 | 311(6.37%)b | 1.45% | 0.39% | |
| Diabetes | Poulton et al, 2018 [53] | 25,249 | 817(3.24%) | 175 | 4(2.29%) | 4881 | 122(2.50%)b | −0.95% | −0.74% |
| Postpartum hemorrhage | Poulton et al, 2018 [53] | 10749 | 169(1.57%) | 78 | 2(2.56%) | 2073 | 35(1.69%)b | 0.99% | 0.12% |
| Placental abruption | Cohen et al, 2017 [47] | 1461493 | 20676(1.41%) | 4846 | 88(1.82%) | 453 | 11(2.42%)a | 0.41% | 1.01% |
| Labour and delivery outcomes | |||||||||
| Spontaneous abortion | Haervig et al, 2014 [49] | 1054014 | 114389(10.86%) | 480 | 54(11.25%) | 706 | 83 (11.76%)c | 0. 39% | 0.90% |
| Bro et al, 2015 [46] | 989471 | 114672(11.59%) | 186 | 18(9.67%) | 275 | 26(9.45%)d | −1.92% | −2.14% | |
| Diav-Citrin et al, 2016 [48] | 382 | 27(7.07%) | 383 | 54(14.10) | - | - | 7.03% | - | |
| Instrumental vaginal delivery | Poulton et al, 2018 [53] | 25225 | 3677(14.57%) | 175 | 31(17.71%) | 4878 | 692(14.19%)b | 3.14% | −0.38% |
| Caesarean delivery | Poulton et al, 2018 [53] | 25237 | 5564(22.04%) | 175 | 52(29.71%) | 4880 | 1266(25.94%) b | 7.67% | 3.90% |
| Active neonatal resuscitation | Poulton et al, 2018 [53] | 20750 | 1683(8.11%) | 159 | 21(13.21%) | 3992 | 394(9.87%) b | 5.10% | 1.76% |
| Preterm birth/gestational age | Bro et al, 2015 [46] | 989471 | 34211(3.46%) | 186 | 3(1.61%) | 275 | 10(3.64%)d | −1.85% | 0.18% |
| Diav-Citrin et al, 2016 [48] | 343 | 23(6.71%) | 293 | 26(8.87%) | - | - | 2.16% | - | |
| Cohen et al, 2017 [47] | 1461493 | 163772(11.21%) | 4846 | 635(13.10%) | 453 | 56(12.36%)a | 1.89% | 1.15% | |
| Nörby et al, 2017 [51] | 953668 | 52182(5.47%) | 1591 | 144(9.05%) | 9475 | 682(7.20%)e | 3.58% | 1.73% | |
| Poulton et al, 2018 [53] | 25245 | 1832(7.26%) | 175 | 19(10.86%) | 4880 | 403(8.26%)b | 3.60% | 1.00% | |
| Low birth weight | Bro et al, 2015 [46] | 989471 | 23691(2.39%) | 186 | 1 (1.98%) | 275 | 8(2.90%)d | −0.41% | 0.51% |
| Poulton et al, 2018 [53] | 25235 | 1676 (6.64%) | 175 | 20(11.43%) | 4873 | 353(7.24%) b | 4.79% | 0.60% | |
| Small for gestational age | Bro et al, 2015 [46] | 989471 | 65499(6.62%) | 186 | 4(2.15%) | 275 | 18(6.55%)d | −4.47% | −0.07% |
| Cohen et al, 2017 [47] | 1451493 | 42526(2.92%) | 4846 | 178(3.67%) | 453 | 20(4.42%)a | 0.75% | 1.46% | |
| Nörby et al, 2017 [51] | 953668 | 21789(2.28%) | 1591 | 43(2.70%) | 9475 | 222(2.34%)e | 0.42% | 0.06% | |
| Large for gestational age | Nörby et al, 2017 [51] | 953668 | 39273(4.11%) | 1591 | 78(4.90%) | 9475 | 422(4.50%) e | 0.79% | 0.39% |
| High birth weight | Poulton et al, 2018 [53] | 25235 | 2539(10.06%) | 175 | 20(11.43%) | 4873 | 481(9.87%)b | 1.37% | −0.19% |
| Low Apgar scores | Bro et al, 2015 [46] | 989471 | 50184(5.07%) | 186 | 8(4.30%) | 275 | 8(2.91%)d | −0.77% | −2.16% |
| Nörby et al, 2017 [51] | 953668 | 12592(1.32%) | 1591 | 38(2.38%) | 9475 | 177(1.86%)e | 1.06% | 0.54% | |
| Poulton et al, 2018 [53] | 25179 | 640(2.54%) | 174 | 5(2.87%) | 4767 | 133(2.79%) b | 0.33% | 0.25% | |
| Stillbirth/perinatal death | Haervig et al, 2014 [49] | 1054014 | 3677(0.35%) | 480 | 2(0.42%) | 706 | 1(0.14%)c | 0.07% | −0.21% |
| Bro et al, 2015 [46] | 989471 | 3517(0.36%) | 186 | 0 | 275 | 1(0.04%) d | −0.36% | −0.32% | |
| Nörby et al, 2017 [51] | 953668 | 4268(0.45%) | 1591 | 8(0.50%) | 9475 | 38(0.41%) e | 0.05% | −0.04% | |
| Poulton et al, 2018 [53] | 25233 | 233(0.92%) | 175 | 2(1.14%) | 4870 | 47(0.97%) b | 0.22% | 0.05% | |
| NICU admission | Nörby et al, 2017 [51] | 953668 | 79530(8.34%) | 1591 | 259(16.27%) | 9475 | 1105(11.66%) e | 7.93% | 3.32% |
| Poulton et al, 2018 [53] | 25239 | 4305(17.06%) | 175 | 47(26.9%) | 4879 | 1019(20.89%) b | 9.84% | 3.83% | |
| Congential malformations | |||||||||
| Major malformation | Haervig et al, 2014 [49] | 1054014 | 41238(3.91%) | 480 | 3(0.63%) | - | - | −3.28% | - |
| Pottegard et al, 2014 [52] | 2220 | 86(3.87%) | 222 | 7(3.15%) | - | - | −0.72% | - | |
| Bro et al, 2015 [46] | 989471 | 39557(4.00%) | 186 | 2(1.08%) | 275 | 7(2.55%) d | −2.92% | 1.45% | |
| Diav-Citrin et al, 2016 [48] | 358 | 13(3.6%) | 309 | 10(3.23%) | - | - | −0.41% | - | |
| Nörby et al, 2017 [51] | 953668 | 20736(2.17%) | 1591 | 48(3.02%) | 9475 | 205(2.16%) e | 0.85% | −0.01% | |
| Huybrechts et al, 2018 [50] | 1797938 | 62966(3.50%) | 7643 | 348(4.55%) | - | - | 1.05% | - | |
| Cadiovascular malformation | Pottegard et al, 2014 [52] | 2220 | 32(1.44%) | 222 | 3(1.35%) | - | - | −0.09% | - |
| Diav-Citrin et al, 2016 [48] | 358 | 3 (0.84%) | 247 | 2(0.81%) | - | - | −0.03% | - | |
| Huybrechts et al, 2018 [50] | 1797938 | 22910(1.27%) | 7643 | 125(1.63%) | - | - | 0.36% | - | |
| Other perinatal morbidity among infants | |||||||||
| Respiratory disorders | Nörby et al, 2017 [51] | 953668 | 35479(3.72%) | 1591 | 92(5.78%) | 9475 | 511(5.39%) e | 2.06% | 1.67% |
| Hyperbilirubinemia | Nörby et al, 2017 [51] | 953668 | 42948(4.50%) | 1591 | 91(5.71%) | 9475 | 511(5.39%) e | 1.21% | 0.89% |
| Hypoglycemia | Nörby et al, 2017 [51] | 953668 | 23965(2.51%) | 1591 | 66(4.15%) | 9475 | 326(3.44%) e | 1.64% | 0.93% |
| Feeding difficulties | Nörby et al, 2017 [51] | 953668 | 9837(1.03%) | 1591 | 34(2.14%) | 9475 | 130(1.37%) e | 1.11% | 0.34% |
| CNS-related disorders | Nörby et al, 2017 [51] | 953668 | 2885(0.30%) | 1591 | 16(1.01%) | 9475 | 40(0.42%) e | 0.71% | 0.12% |
| Withdrawal symptoms for therapeutic drugs | Nörby et al, 2017 [51] | 953668 | 124(0.01%) | 1591 | 7(0.44%) | 9475 | 10(0.11%) e | 0.43% | 0.10% |
ADHD: Attention deficit/hyperactivity disorder
NICU: Neonatal intensive care unit
Alternative comparison groups including:
a
Women exposed to Atomoxetine (a non-stimulant ADHD medication) during pregnancy;
b
Women who used ADHD medication before or after pregnancy;
c
Women with discordant exposure to ADHD medication across pregnancies;
d
Women diagnosed with ADHD who did not take ADHD medications;
e
Women who used ADHD medication before or after pregnancy only.