Risk of neurodevelopmental disorders associated with prenatal exposure to seasonal inactivated influenza vaccine among children <5 years of age, by trimester of prenatal vaccination
| Unexposed to seasonal influenza vaccine during pregnancy (n=124 851) (n=122 385)* | Exposed to seasonal influenza vaccine during pregnancy (n=15 663) (n=15 272)* | Trimester of vaccine exposure | |||
| First trimester (n=3034) (n=2959)* | Second trimester (n=6014) (n=5896)* | Third trimester (n=6615) (n=6417)* | |||
| Neurodevelopmental disorder | |||||
| Cases, n (%) | 6710 (5.4) | 726 (4.6) | 143 (4.7) | 304 (5.1) | 279 (4.2) |
| Unweighted HR (95% CI) | 1 (reference) | 1.01 (0.94 to 1.09) | 1.02 (0.87 to 1.21) | 1.03 (0.92 to 1.15) | 0.99 (0.88 to 1.12) |
| Cases, n (%) | 6594 (5.4) | 713 (4.7) | 140 (4.7) | 299 (5.1) | 274 (4.3) |
| Weighted HR (95% CI)† | 1 (reference) | 1.00 (0.91 to 1.08) | 0.99 (0.82 to 1.18) | 1.04 (0.91 to 1.18) | 0.95 (0.83 to 1.09) |
| Mental or behavioural disorder | |||||
| Cases, n (%) | 456 (0.4) | 49 (0.3) | 7 (0.2) | 24 (0.4) | 18 (0.3) |
| Unweighted HR (95% CI) | 1 (reference) | 1.02 (0.76 to 1.37) | 0.75 (0.36 to 1.58) | 1.21 (0.80 to 1.83) | 0.95 (0.59 to 1.52) |
| Cases, n (%) | 447 (0.4) | 47 (0.3) | 6 (0.2) | 24 (0.4) | 17 (0.3) |
| Weighted HR (95% CI)† | 1 (reference) | 0.97 (0.70 to 1.35) | 0.69 (0.29 to 1.63) | 1.19 (0.75 to 1.88) | 0.91 (0.54 to 1.54) |
| Neurological disorder | |||||
| Cases, n (%) | 6399 (5.1) | 694 (4.4) | 139 (4.6) | 290 (4.8) | 265 (4.0) |
| Unweighted HR (95% CI) | 1 (reference) | 1.02 (0.94 to 1.10) | 1.04 (0.88 to 1.24) | 1.03 (0.92 to 1.16) | 0.99 (0.88 to 1.12) |
| Cases, n (%) | 6291 (5.1) | 683 (4.5) | 137 (4.6) | 285 (4.8) | 261 (4.1) |
| Weighted HR (95% CI)† | 1 (reference) | 1.00 (0.91 to 1.09) | 1.00 (0.83 to 1.20) | 1.04 (0.91 to 1.19) | 0.95 (0.83 to 1.10) |
| Seizure disorder | |||||
| Cases, n (%) | 2744 (2.2) | 311 (2.0) | 52 (1.7) | 132 (2.2) | 127 (1.9) |
| Unweighted HR (95% CI) | 1 (reference) | 0.99 (0.88 to 1.11) | 0.84 (0.64 to 1.11) | 1.03 (0.87 to 1.23) | 1.01 (0.85 to 1.21) |
| Cases, n (%) | 2695 (2.2) | 303 (2.0) | 50 (1.7) | 127 (2.2) | 126 (2.0) |
| Weighted HR (95% CI)† | 1 (reference) | 0.99 (0.87 to 1.14) | 0.73 (0.54 to 0.998) | 1.10 (0.90 to 1.35) | 1.00 (0.81 to 1.22) |
| Sleep disorder | |||||
| Cases, n (%) | 3369 (2.7) | 327 (2.1) | 72 (2.4) | 134 (2.2) | 121 (1.8) |
| Unweighted HR (95% CI) | 1 (reference) | 0.98 (0.88 to 1.11) | 1.12 (0.89 to 1.42) | 0.96 (0.81 to 1.14) | 0.96 (0.80 to 1.15) |
| Cases, n (%) | 3317 (2.7) | 325 (2.1) | 72 (2.4) | 134 (2.3) | 119 (1.9) |
| Weighted HR (95% CI) | 1 (reference) | 0.97 (0.85 to 1.10) | 1.11 (0.86 to 1.42) | 0.96 (0.80 to 1.16) | 0.91 (0.74 to 1.11) |
Bold values indicate statistically significant associations.
All outcomes were identified from ICD-10-AM codes found in the principal and 20 additional diagnosis fields of hospital inpatient and emergency department presentation records, and from the presenting symptom code found in the emergency department presentation records (online supplemental table 2).
*Sample size after trimming the 1st and 99th percentile of the predicted probability of vaccination.
†HRs were weighted by trimmed inverse-probability of treatment weights factoring for maternal covariates including age, Aboriginal status, socioeconomic status, body mass index, parity, pre-existing medical conditions (asthma, essential hypertension, pre-existing diabetes), pregnancy complications (gestational diabetes, gestational hypertension, pre-eclampsia), smoking status during pregnancy, trimester at the first prenatal care visit, year and season of birth.
ICD-10-AM, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification.