Table 4.
Safety of maternal antenatal pertussis vaccine
| Study design | Intervention/exposure type, mean gestational week at vaccination (range) | Compara-tor | Vaccine group | Control group | Crude RR (95% CI) | Adjusted RR (95% CI) | |||
|---|---|---|---|---|---|---|---|---|---|
| Event n. (%) | N | Event n. (%) | N | ||||||
| ADVERSE EVENTS (AE) | |||||||||
| Any solicited adverse events | |||||||||
| Hoang [30]a | RCT | Tdap 26 (19–35) | TT | 23 (44.2) | 52 | 22 (43.1) | 51 | 1.0 (0.7–1.6) | |
| Munoz [31]b | RCT | Tdap -- (30–32) | placebo | 26 (78.8) | 33 | 5 (33.3) | 15 | 2.4 (1.1–4.9) | |
| Any injection site reactions | 26 (78.8) | 33 | 3 (20.0) | 15 | 3.9 (1.4–11.0) | ||||
| (pain) | 25 (75.8) | 33 | 2 (13.3) | 15 | 5.7 (1.5–20.9) | ||||
| (erythema/redness) | 3 (9.1) | 33 | 1 (6.7) | 15 | 1.4 (0.2–12.1) | ||||
| (induration/swelling) | 3 (9.1) | 33 | 0 (0) | 15 | NAc | ||||
| Any systemic symptoms | 12 (36.4) | 33 | 3 (20.0) | 15 | 1.8 (0.6–5.5) | ||||
| (fever) | 1 (3.0) | 33 | 0 (0) | 15 | NAc | ||||
| (headache) | 11 (33.3) | 33 | 3 (20.0) | 15 | 1.7 (0.5–5.1) | ||||
| (malaise) | 4 (12.1) | 33 | 2 (13.3) | 15 | 0.9 (0.2–4.4) | ||||
| (myalgia) | 5 (15.2) | 33 | 0 (0) | 15 | NAc | ||||
| OBSTETRIC COMPLICATIONS | |||||||||
| Hypertensive disorders | |||||||||
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | 22 (0.4) | 6185 | 54 (0.3) | 18,523 | 1.2 (0.7–2.0) | |
| Kharbanda [24] | RCS | Tdap, before 20 | no vaccine | 497 (8.2) | 6083 | 7736 (8.0) | 97,265 | 1.0 (0.9–1.1) | 1.1 (1.0–1.2)e |
| Maertens [29]d | PCS | Tdap 29 (22–33) | no vaccine | 6 (10.5) | 57 | 2 (4.9) | 41 | 2.2 (0.5–10.2) | |
| Premature contraction | |||||||||
| Hoang [30] | RCT | Tdap 26 (19–35) | TT | 2 (3.8) | 52 | 1 (2.0) | 51 | 2.0 (0.2–21.0) | |
| Maertens [29] | PCS | Tdap 29 (22–33) | no vaccine | 4 (7.0) | 57 | 0 (0) | 41 | NAc | |
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | 5 (0.1) | 6185 | 21 (0.1) | 18,523 | 0.7 (0.3–1.9) | |
| Chorioamnionitis | |||||||||
| Kharbanda [24] | RCS | Tdap -- (anytime) | no vaccine | 1596 (6.1) | 26,229 | 5329 (5.5) | 97,265 | 1.11 (1.05–1.17) | 1.2 (1.13–1.3)e |
| (subset) | Tdap, 27–36 | 637 (0.1) | 11,351 | 5329 (0.1) | 97,265 | 1.02 (0.95–1.11) | 1.1 (1.0–1.2) e | ||
| Proteinuria | |||||||||
| Kharbanda [25]f | RCS | Tdap -- (anytime) | no vaccine | 84 (0.2) | 53,885 | 207 (0.2) | 109,253 | 0.8 (0.6–1.1) | 0.8 (0.6–1.1)g |
| Caesarean section | |||||||||
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | 1238 (20.0) | 6185 | 3748 (20.2) | 18,523 | 1.0 (0.9–1.0) | |
| Postpartum haemorrhage | |||||||||
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | 59 (1.0) | 6185 | 181 (1.0) | 18,523 | 1.0 (0.7–1.3) | |
| Venous thromboembolism | |||||||||
| Kharbanda [25]f | RCS | Tdap -- (anytime) | no vaccine | 22 (0.04) | 53,885 | 69 (0.1) | 109,253 | 0.6 (0.4–1.0) | 0.7 (0.4–1.1)g |
| Thrombocytopenia | |||||||||
| Kharbanda [25]f | RCS | Tdap, ≥ 20 | no vaccine | 249 (0.1) | 44,063 | 579 (0.1) | 86,057 | 0.8 (0.7–1.0) | 0.9 (0.7–1.0)g |
| Gestational diabetes | |||||||||
| Kharbanda [25]f | RCS | Tdap, ≥ 20 | no vaccine | 1101 (2.5) | 44,063 | 2263 (2.6) | 86,057 | 1.0 (0.9–1.0) | 1.0 (0.9–1.0)g |
| Cardiac events | |||||||||
| Kharbanda [25]f | RCS | Tdap, ≥ 20 | no vaccine | 90 (0.2) | 44,063 | 198 (0.2) | 86,057 | 0.9 (0.7–1.1) | 0.9 (0.7–1.2)g |
| Oligohydramnios | |||||||||
| Maertens [29] | PCS | Tdap 29 (22–33) | no Tdap | 1 (1.8) | 57 | 0 (0) | 41 | NAc | |
| Placenta praevia | |||||||||
| Maertens [29] | PCS | Tdap 29 wks (22–33) | no vaccine | 0 (0) | 57 | 1 (2.44) | 41 | 0 (NA)c | |
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | 2 (< 0.1) | 6185 | 15 (0.1) | 18,523 | 0.4 (0.1–1.7) | |
| PERINATAL COMPLICATIONS | |||||||||
| Stillbirth | |||||||||
| Hoang [30] | RCT | Tdap 26 (19–35) | TT | 0 (0) | 52 | 1 (2.0) | 51 | 0 (NA)c | |
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | 12 (0.2) | 6185 | 42 (0.2) | 18,523 | 0.9 (0.5–1.6) | |
| Shakib [36] | RCS | Tdap -- (anytime) | no vaccine | 0 (0) | 138 | 5 (0.9) | 552 | 0 (NA)c | |
| Neonatal death | |||||||||
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | 2 (<0.1) | 6185 | 6 (<0.1) | 18,523 | 1.0 (0.2–4.9) | |
| Preterm births | |||||||||
| Munoz [31] | RCT | Tdap -- (30–32) | no vaccine | 3 (9.1) | 33 | 1 (6.7) | 15 | 1.4 (0.2–12.1) | |
| Hoang [30] | RCT | Tdap 26 (19–35) | TT | 0 (0) | 52 | 1 (2.0) | 51 | 0 (NA)c | |
| Kharbanda [24] | RCS | Tdap -- (anytime) | no vaccine | 1527 (5.8) | 26,229 | 7544 (7.8) | 97,265 | 0.8 (0.7–0.8)h | 1.0 (1.0–1.1)e |
| Shakib [36] | RCS | Tdap -- (anytime) | no vaccine | 8 (6.0) | 134 | 38 (7.5) | 505 | 0.8 (0.4–1.7) | |
| SGA (<10th percentile) | |||||||||
| Kharbanda [24] | RCS | Tdap -- (anytime) | no vaccine | 2214 (8.4) | 26,229 | 8086 (8.3) | 97,265 | 1.0 (1.0–1.0) | 1.0 (1.0–1.1)e |
| Low birth weight (< 2500 g) | |||||||||
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | 126 (2.0) | 6185 | 311 (1.7) | 18,523 | 1.2 (1.0–1.5) | |
| Birth weight (kg) | |||||||||
| Munoz [29] | RCT | Tdap -- (30–32) | placebo | Mean 3.2 (SD 0.5) | 33 | Mean 3.5 (SD 0.7) | 15 | MD −0.3 (−0.7–0.1) | |
| Donegan [32] | RCS | Any pertussis vaccine--(anytime) | no vaccine | Median 3.5 | 6185 | Median 3.5 | 18,523 | Median difference 0 | |
| Apgar scores 1 min | |||||||||
| Munoz [31] | RCT | Tdap -- (30–32) | no vaccine | Mean 8.0 (SD 1.4) | 33 | Mean 7.9 (SD 1.1) | 15 | MD 0.1(−0.07–0.9) | |
| Apgar scores 5 min | |||||||||
| Munoz [31] | RCT | Tdap -- (30–32) | no vaccine | Mean 8.9 (SD 0.2) | 33 | Mean 8.9 (SD 0.4) | 15 | MD 0 (−0.2–0.2) | |
| Abnormal conditions | |||||||||
| Munoz [31] | RCT | Tdap -- (30–32) | no vaccine | 3 (9.1)i | 33 | 3 (20.0)j | 15 | 0.5 (0.1–2.0) | |
| Congenital anomalies | |||||||||
| Munoz [31] | RCT | Tdap -- (30–32) | no vaccine | 1 (3.0)k | 33 | 2 (13.3)l | 15 | 0.2 (0.0–2.3) | |
RCT Randomised control trial, RCS Retrospective cohort study, RR Risk ratio, CI Confidence interval, MD mean difference (associated CI calculated based on a t-distribution), SD standard deviation, SGA Small-for-gestational-age, Tdap tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine, TT tetanus toxoid; no vaccine, not receiving Tdap or pertussis-containing vaccine during pregnancy, NA not applicable
aEvents occurred within 30 days after injection
bEvents occurred within 7 days after injection
cConfidence interval cannot be calculated when one of the rates is zero
dPreterm and term pre-eclampsia, and hypertension counted as hypertensive disorders
eAdjusted for receipt of influenza vaccine, study site, and propensity score (which included sociodemographic characteristics [neighbourhood poverty index, age], presence of maternal comorbidities [hypertension, diabetes and cardiovascular or renal disease occurring prior to the start of pregnancy], receipt of medical care in the first trimester, and number of hospitalisations during the first 20 weeks of pregnancy as a surrogate of pregnancy complications)
fEvents occurred within 42 days after injection
gAdjusted for patterns of care prior to vaccination date/index date, perinatal care utilisation (as measured with the Kotelchuck Adequacy of Prenatal Care Utilization Index) and having an inpatient encounter before the vaccination date/index date
hThe crude risk ratio presented here is not the value the original authors reported. Instead, the researcher of this review recalculated it. This correction was made based on the numbers of events (preterm births) in both Tdap-vaccinated and unvaccinated groups, as reported in the original article
iAbnormal conditions at infant initial examination: Cephalohematoma (n = 2) and hydrocele (n = 1)
jDecreased breath sounds with increased anteroposterior diameter (n = 1), laceration (n = 1), large for gestational age and heart murmur (n = 1)
kBilateral renal pelviectasis (n = 1)
1Asymptomatic atrial or ventricular septal defect (n = 1) and cardiomyopathy (n = 1)