BACKGROUND AND OBJECTIVES

Infant influenza and pertussis disease causes considerable morbidity and mortality worldwide. We examined the effectiveness of maternal influenza and pertussis vaccines in preventing these diseases in infants.

METHODS

This inception cohort study comprised women whose pregnancies ended between September 1, 2015, and December 31, 2017, in Victoria, Australia. Maternal vaccination status was sourced from the Victorian Perinatal Data Collection and linked to 5 data sets to ascertain infant outcomes and vaccination. The primary outcome of interest was laboratory-confirmed influenza or pertussis disease in infants aged <2 months, 2 to <6 months, and <6 months combined. Secondary outcomes included infant hospitalization (emergency presentation or admission) and death. Risk ratios and 95% confidence intervals (CIs) were estimated by Poisson regression. Vaccine effectiveness (VE) was estimated as (1 minus the risk ratio) x 100%.

RESULTS

Among 186 962 pregnant women, 85 830 (45.9%) and 128 060 (68.5%) were vaccinated against influenza and pertussis, respectively. There were 175 and 51 infants with laboratory-confirmed influenza and pertussis disease, respectively. Influenza VE was 56.1% (95% CI, 23.3% to 74.9%) for infants aged <2 months and 35.7% (2.2% to 57.7%) for infants aged 2 to <6 months. Pertussis VE was 80.1% (95% CI, 37.1% to 93.7%) for infants aged <2 months and 31.8% (95% CI, −39.1% to 66.6%) for infants aged 2 to <6 months.

CONCLUSIONS

Our study provides evidence of the direct effectiveness of maternal influenza and pertussis vaccination in preventing these diseases in infants aged <2 months. The findings strengthen the importance of maternal vaccination to prevent these diseases in infants.

What’s Known on This Subject:

Vaccination of women during pregnancy is recommended to prevent infant influenza and pertussis infections. Previous studies have suggested that maternal vaccination can reduce the risk of infant influenza by 48% to 80% and pertussis by 68% to 95%.

What This Study Adds:

In this population-wide inception cohort study comprising 186 962 mother-infant pairs, we found maternal influenza and pertussis vaccination significantly reduced the risk of laboratory-confirmed disease among infants aged <2 months. Vaccine effectiveness estimates were 56.1% for influenza and 80.1% for pertussis.

Influenza and pertussis infections cause substantial morbidity and mortality worldwide, and their prevention remains a global public health challenge.13  Both infections disproportionately affect pregnant women and infants. Vaccination during pregnancy (maternal vaccination) has been shown to be an effective strategy to reduce the risks of these infections in infants.410  Despite this, uptake of influenza and pertussis vaccines during pregnancy is variable,11  and the monitoring of effectiveness at a local level is required.

In Australia, funded maternal influenza and pertussis vaccines were introduced as part of the National Immunization Program in 2010 and 2018, respectively.12  The influenza vaccine is recommended at any stage during pregnancy (optimally before the onset of influenza season), and pertussis vaccine is recommended between 20 and 32 weeks’ gestation.13  These can be administered by medical practitioners, nurse immunizers, or pharmacists registered under the Victorian Pharmacist-Administered Vaccination Program.14  The objective is to protect infants from these infections in the first few months of life and before infants can receive active immunization themselves. Globally, there are no influenza vaccines licensed for use in infants before 6 months of age,1  and, in Australia, infants are recommended to receive pertussis-containing vaccines at 2, 4, and 6 months of age (with the first dose able to be received as early as 6-weeks) and an additional 2 doses at 18 months and four-years of age.12  Similar maternal vaccination programs have been implemented elsewhere including New Zealand, the United Kingdom, the United States, Belgium, Spain, and Argentina.1520  Coverage varies, with published estimates suggesting higher uptake of pertussis vaccine than influenza vaccine among pregnant women.11,15,16,20,21 

Evidence of the effectiveness of maternal vaccines in reducing infant infection is mounting. Maternal influenza vaccination has been shown to reduce infant influenza by between 48% and 80%.4,6,10,22,23  Several observational studies have revealed that maternal pertussis vaccination can reduce the risk of pertussis disease, hospitalization, or death among infants by between 69% and 95%.24  However, in a systematic review, researchers suggested that these studies have a moderate to high risk of bias, with selection bias, imprecise outcome definitions, and residual confounding cited as potentially affecting the validity of the vaccine effectiveness (VE) estimates.24  The assessment of the effectiveness of maternal vaccines in the real-world setting continues to be required. We examined the effectiveness of the maternal influenza and pertussis vaccines in preventing these infections in infants aged <6 months in the state of Victoria, the southern-most mainland state of Australia, with a population of 6 million and nearly 80 000 births per year.25 

We conducted a record-linkage inception cohort study using 6 population-wide data sets. The primary cohort comprised pregnant women captured in the Victorian Perinatal Data Collection (VPDC) whose pregnancies ended between September 1, 2015, and December 31, 2017. The VPDC contains information on obstetric conditions, procedures, and pregnancy and birth outcomes relating to all registrable live births and stillbirths in Victoria. It captures information relevant to the pregnancy or birth, including procedures undertaken (such as the administration of influenza and pertussis vaccines) outside the hospital of birth. Variables extracted from this data set included maternal influenza and pertussis vaccination status (vaccinated at any time during the current pregnancy and recorded as yes, no, or missing for each condition of interest; the timing of vaccination relative to gestational age is not captured), sociodemographic data, parity, whether the pregnancy was multiple, the pregnancy end date, the gestational age at birth, discipline of antenatal care provider, breastfeeding, maternal medical conditions, and obstetric complications. Infant variables included birth weight, Apgar score, and admission into special or intensive care nursery.

The primary cohort was linked with 5 secondary data sets to ascertain the outcomes and primary vaccination status of the infants born to these women: (1) Public Health Event Surveillance System (PHESS); (2) Victorian Emergency Minimum Dataset (VEMD); (3) Victorian Admitted Episodes Dataset (VAED); (4) Victorian Death Index (VDI); and (5) Australian Immunisation Register (AIR). The PHESS is used to capture notifiable events of public health importance in Victoria, including laboratory-confirmed cases of influenza and pertussis, which are required to be notified by medical practitioners and laboratories.26  The VEMD and VAED are administrative data sets used to capture all public emergency department (ED) presentations and all public and private hospital admissions in Victoria, respectively. The VDI is used to capture all registrable deaths occurring in Victoria,27  and the AIR is a national data set capturing information about vaccines (including antigen and administration date) administered to all Australian residents.28 

Record linkages were conducted by the Centre for Victorian Data Linkages at the Victorian Government Department of Health. Several data cleaning and enrichment steps were conducted as part of this process. First, the VPDC was enriched with infant names sourced from the Victorian Birth Registry. To achieve this, deterministic linkage was conducted by using mother's name, mother’s date of birth, infant’s date of birth, and birth order from the VPDC. Second, all data sets were enriched by imputing missing data pertaining to sex of the infant from infant’s name. Proprietary logic embedded within SAS DataFlux (SAS Institute, Inc, Cary, NC) was used to achieve this.29  The linkage process on enriched data sets involved a deterministic linkage approach linking the combined mother-infant record from the primary cohort with infant records contained in the secondary data sets by using several identifying variables (Supplemental Information).

The key exposure of interest was the receipt of a maternal influenza or pertussis vaccine during pregnancy. This data item has been routinely captured in the VPDC since June 2015, when the state-based maternal pertussis vaccination program was implemented. Midwives collect the data at or around the time of vaccination or birth by using a combination of medical records or self-report from the pregnant woman. The date and brand of the vaccine administered is not collected; however, assumptions about the vaccines administered to pregnant women can be inferred from the availability and composition of these vaccines during the study period (Supplemental Information). Women whose infants were notified with influenza and pertussis and had a missing vaccination record on the VPDC were augmented with maternal vaccination data captured on PHESS. To assess the uptake of these vaccines during pregnancy, data were analyzed as unique pregnancies. To assess VE, data were analyzed as mother-infant pairs, whereby the vaccination status for women bearing multiples was carried over for all infants born to these women.

The primary outcome measure was laboratory-confirmed influenza or pertussis notification among infants aged <2 months, 2 to <6 months, and combined (aged <6 months). The stratification enabled evaluation of VE in vaccine naïve infants <2 months of age who had not yet received ≥1 pertussis-containing vaccines as part of the infant primary vaccination schedule, as well as any modifications in VE at the latter time point. Only cases meeting the national surveillance case definition for influenza and pertussis were included.30  Two secondary outcomes were assessed: (1) any influenza or pertussis event, defined as the first disease-specific ED presentation or hospitalization, laboratory-confirmed disease-specific notification, or disease-specific mortality (Supplemental Table 6) and (2) severe disease, defined as disease-specific hospitalization or death31  (Supplemental Table 7).

All pregnant women were included in the analysis of maternal vaccination coverage. In the analyses of VE, we excluded pregnancies ending in stillbirth. For the assessment of maternal pertussis VE, we excluded pregnancies ending <30 weeks’ gestation to align with the recommendations for maternal pertussis vaccination (from 28 weeks’ gestation)13  relevant to the study period.

Crude and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) were estimated by using Poisson regression models for each outcome of interest.32  The models were developed incorporating the following known and plausible confounding factors on the basis of previous research11 : maternal Aboriginal and Torres Strait Islander status, maternal country of birth, maternal smoking status during pregnancy, primiparity, whether the birth was a multiple, discipline of the antenatal care provider, gestational age at first antenatal visit, gestational week of birth, and any preexisting maternal medical condition or obstetric complication (Supplemental Table 8). Because uptake of the maternal vaccines and incidence of infant disease varied over time, a temporal component was also included in the adjusted models. For influenza, we adjusted for calendar quarter of birth (regardless of the year), and, for pertussis, we adjusted for the time of birth in four-monthly groups from September to December 2015, to September to December 2017. VE was estimated by using the formula: VE = (1 − aRR) × 100%, where aRR is the aRRs of infants with the outcomes of interest whose birth mother was vaccinated during pregnancy, compared with those whose birth mother was not vaccinated. For each condition, we calculated the number of notified cases avoided through vaccination using the following formula:

navoid=VE×nu100

where nu is the number of unvaccinated cases and VE is the vaccine effectiveness.

We also developed an expanded Cox model to assess epidemiological evidence to test the hypothesis that maternal pertussis vaccination may impair protection provided by infant vaccination. The model considered infant pertussis vaccination status as a time-varying covariate, with the time at risk for each infant considered separately by date of infant vaccine: from birth until receipt of the first dose, from the first to the second dose, and after the second dose. The model included an interaction term between maternal vaccination and infant vaccination (Supplemental Table 9). Analyses were performed by using Stata 15.0 (Stata Corp, College Station, TX).

Study approvals were obtained from the Victorian Government Department of Health and Human Services Human Research Ethics Committee (reference 15/17) and Consultative Council for Obstetric and Paediatric Morbidity and Mortality. The study was supported by the Victorian Government Department of Health as part of a vaccine program evaluation, and AIR data were used in accordance with the Australian Immunization Register Act 2015.28 

There were 186 962 mother-infant pairs with pregnancies ending between September 1, 2015, and December 31, 2017. Overall, 85 830 (45.9%) and 128 060 (68.5%) women were vaccinated against influenza and pertussis during pregnancy, respectively. This varied by the month of pregnancy end date, consistent with our previous findings,11  which ranged from 20.1% to 72.0% for influenza and 54.1% to 80.7% for pertussis (data are not shown).

We excluded 834 (<1%) mother-infant pairs ending in stillbirth and 724 (<1%) duplicate mother-infant pairs who were the result of false-positive record linkages, leaving 185 404 included in all subsequent analyses relating to influenza. For pertussis analyses, a further 1210 (<1%) mother-infant pairs whose infants were born before 30 weeks’ gestation were excluded, leaving 184 194 mother-infant pairs included in the analysis (Fig 1). The characteristics of each cohort by vaccination status and infant disease outcomes are shown (Tables 1 and 2).

FIGURE 1

Study flow diagram showing exclusion criteria.

FIGURE 1

Study flow diagram showing exclusion criteria.

Close modal
TABLE 1

Characteristics of Cohort by Maternal Vaccination Status and Laboratory-Confirmed Influenza Notification in Infants (<6 mo; N = 185 404)

Maternal Influenza Vaccination StatusInfant Influenza Notification
Not Vaccinated (n = 86 012), n (%)Vaccinated (n = 85 365), n (%)Missing (n = 14 027), n (%)PNo (n = 185 229), n (%)Yes (n = 175), n (%)P
Vaccinated this pregnancy against influenza       <.001 
 Not vaccinated — — — — 85 901 (99.9) 111 (0.1) — 
 Vaccinated — — — — 85 315 (99.9) 50 (0.1) — 
 Missing or unknown — — — — 14 013 (99.9) 14 (0.1) — 
Maternal age, y    <.001   .041 
 <18 338 (56.6) 217 (36.3) 42 (7.0) — 596 (99.8) 1 (0.2) — 
 18–24 10 179 (53.0) 7687 (40.0) 1334 (6.9) — 19 184 (99.9) 16 (0.1) — 
 25–29 22 919 (48.3) 21 262 (44.8) 3298 (6.9) — 47 449 (99.9) 30 (0.1) — 
 30–34 31 212 (44.4) 33 677 (47.9) 5417 (7.7) — 70 238 (99.9) 68 (0.1) — 
 35–39 17 266 (44.5) 18 408 (47.5) 3117 (8.0) — 38 738 (99.9) 53 (0.1) — 
 ≥40 4092 (45.4) 4113 (45.6) 811 (9.0) — 9009 (99.9) 7 (0.1) — 
 Missing 6 (40.0) 1 (6.7) 8 (53.3) — 15 (100.0) 0 (0.0) — 
Maternal indigenous status    <.001   .47 
 Not indigenous 84 227 (46.2) 84 200 (46.2) 13 813 (7.6) — 182 069 (99.9) 171 (0.1) — 
 Indigenous 1483 (56.9) 1003 (38.5) 120 (4.6) — 2602 (99.8) 4 (0.2) — 
 Unknown 302 (54.1) 162 (29.0) 94 (16.8) — 558 (100.0) 0 (0.0) — 
Country of birth    <.001   .27 
 Australian born 53 492 (46.8) 53 745 (47.0) 7065 (6.2) — 114 185 (99.9) 117 (0.1) — 
 Born overseas 32 120 (45.7) 31 326 (44.6) 6840 (9.7) — 70 228 (99.9) 58 (0.1) — 
 Missing 400 (49.0) 294 (36.0) 122 (15.0) — 816 (100.0) 0 (0.0) — 
Smoked at any time during pregnancy    <.001   .31 
 Did not smoke 73 070 (45.3) 75 601 (46.9) 12 502 (7.8) — 161 021 (99.9) 152 (0.1) — 
 Smoked 9346 (57.5) 5903 (36.3) 1008 (6.2) — 16 245 (99.9) 12 (0.1) — 
 Missing 3596 (45.1) 3861 (48.4) 517 (6.5) — 7963 (99.9) 11 (0.1) — 
Parity    <.001   <.001 
 Multiparas 51 875 (49.7) 44 567 (42.7) 8000 (7.7) — 104 306 (99.9) 136 (0.1) — 
 Primiparas 34 137 (42.2) 40 798 (50.4) 6027 (7.4) — 80 923 (100.0) 39 (0.0) — 
Plurality    <.001   .92 
 Singleton 83 681 (46.4) 83 170 (46.1) 13 498 (7.5) — 180 178 (99.9) 171 (0.1) — 
 Multiple birth 2300 (46.0) 2195 (43.9) 502 (10.0) — 4993 (99.9) 4 (0.1) — 
 Missing 31 (53.4) 0 (0.0) 27 (46.6) — 58 (100.0) 0 (0.0) — 
Discipline of antenatal care provider    <.001   .017 
 No antenatal care provider 388 (78.9) 51 (10.4) 53 (10.8) — 492 (100.0) 0 (0.0) — 
 General practitioner 9798 (42.4) 12 494 (54.1) 822 (3.6) — 23 099 (99.9) 15 (0.1) — 
 Midwife 28 698 (48.2) 26 105 (43.8) 4743 (8.0) — 59 504 (99.9) 42 (0.1) — 
 Obstetrician 46 657 (46.0) 46 355 (45.7) 8350 (8.2) — 101 246 (99.9) 116 (0.1) — 
 Missing 471 (52.9) 360 (40.4) 59 (6.6) — 888 (99.8) 2 (0.2) — 
Gestational age at first antenatal visit    <.001   .23 
 ≥24 wk 6263 (55.9) 3918 (35.0) 1025 (9.1) — 11 201 (100.0) 5 (0.0) — 
 12–23 wk 40 795 (48.3) 37 051 (43.8) 6687 (7.9) — 84 457 (99.9) 76 (0.1) — 
 ≤11 wk 38 107 (43.2) 43 985 (49.9) 6057 (6.9) — 88 057 (99.9) 92 (0.1) — 
 Missing 847 (55.9) 411 (27.1) 258 (17.0) — 1514 (99.9) 2 (0.1) — 
Gestational age at birth, wk    <.001   .079 
 <28 471 (63.9) 155 (21.0) 111 (15.1) — 736 (99.9) 1 (0.1) — 
 28–36 6770 (48.2) 5896 (42.0) 1367 (9.7) — 14 012 (99.9) 21 (0.1) — 
 ≥37 78 771 (46.2) 79 314 (46.5) 12 549 (7.4) — 170 481 (99.9) 153 (0.1) — 
Any preexisting maternal medical conditiona 1276 (1.5) 1401 (1.6) 278 (2.0) <.001 2951 (1.6) 4 (2.3) .46 
Any obstetric complicationb 22 584 (26.3) 21 728 (25.5) 2839 (20.2) <.001 47 110 (25.4) 41 (23.4) .54 
Maternal admission to HDU or ICU    <.001   .81 
 Not admitted 84 459 (46.4) 84 025 (46.1) 13 693 (7.5) — 182 004 (99.9) 173 (0.1) — 
 Admitted 1504 (48.9) 1298 (42.2) 275 (8.9) — 3075 (99.9) 2 (0.1) — 
 Missing 49 (32.7) 42 (28.0) 59 (39.3) — 150 (100.0) 0 (0.0) — 
Apgar score at 5 min    <.001   .83 
 0–3 331 (56.2) 183 (31.1) 75 (12.7) — 589 (100.0) 0 (0.0) — 
 4–6 1401 (47.7) 1285 (43.8) 249 (8.5) — 2932 (99.9) 3 (0.1) — 
 ≥7 84 102 (46.3) 83 795 (46.1) 13 674 (7.5) — 181 399 (99.9) 172 (0.1) — 
 Missing 178 (57.6) 102 (33.0) 29 (9.4) — 309 (100.0) 0 (0.0) — 
Birth wt, g    <.001   .029 
 <1500 1011 (57.0) 494 (27.8) 269 (15.2) — 1769 (99.7) 5 (0.3) — 
 1500–<2500 5008 (49.1) 4259 (41.7) 937 (9.2) — 10 190 (99.9) 14 (0.1) — 
 ≥2500 79 965 (46.1) 80 597 (46.5) 12 806 (7.4) — 173 212 (99.9) 156 (0.1) — 
 Missing 28 (48.3) 15 (25.9) 15 (25.9) — 58 (100.0) 0 (0.0) — 
Infant admission to SCN or ICU    <.001   .024 
 Not admitted 69 014 (46.2) 69 208 (46.3) 11 112 (7.4) — 149 202 (99.9) 132 (0.1) — 
 Admitted 14 708 (47.1) 13 724 (43.9) 2797 (9.0) — 31 196 (99.9) 33 (0.1) — 
 Missing 2290 (47.3) 2433 (50.3) 118 (2.4) — 4831 (99.8) 10 (0.2) — 
Infant feeding in hospital    <.001   .68 
 Exclusively breastfed 29 509 (47.3) 27 791 (44.6) 5076 (8.1) — 62 313 (99.9) 63 (0.1) — 
 Nonexclusively breastfed 54 960 (45.9) 56 365 (47.1) 8429 (7.0) — 119 646 (99.9) 108 (0.1) — 
 Missing 1543 (47.1) 1209 (36.9) 522 (15.9) — 3270 (99.9) 4 (0.1) — 
Infant quarter of birth    <.001   <.001 
 January to March 24 679 (61.8) 11 738 (29.4) 3513 (8.8) — 39 882 (99.9) 48 (0.1) — 
 April to June 20 651 (52.4) 15 691 (39.8) 3081 (7.8) — 39 355 (99.8) 68 (0.2) — 
 July to September 16 688 (35.6) 26 992 (57.6) 3174 (6.8) — 46 809 (99.9) 45 (0.1) — 
 October to December 23 994 (40.5) 30 944 (52.3) 4259 (7.2) — 59 183 (100.0) 14 (0.0) — 
Maternal Influenza Vaccination StatusInfant Influenza Notification
Not Vaccinated (n = 86 012), n (%)Vaccinated (n = 85 365), n (%)Missing (n = 14 027), n (%)PNo (n = 185 229), n (%)Yes (n = 175), n (%)P
Vaccinated this pregnancy against influenza       <.001 
 Not vaccinated — — — — 85 901 (99.9) 111 (0.1) — 
 Vaccinated — — — — 85 315 (99.9) 50 (0.1) — 
 Missing or unknown — — — — 14 013 (99.9) 14 (0.1) — 
Maternal age, y    <.001   .041 
 <18 338 (56.6) 217 (36.3) 42 (7.0) — 596 (99.8) 1 (0.2) — 
 18–24 10 179 (53.0) 7687 (40.0) 1334 (6.9) — 19 184 (99.9) 16 (0.1) — 
 25–29 22 919 (48.3) 21 262 (44.8) 3298 (6.9) — 47 449 (99.9) 30 (0.1) — 
 30–34 31 212 (44.4) 33 677 (47.9) 5417 (7.7) — 70 238 (99.9) 68 (0.1) — 
 35–39 17 266 (44.5) 18 408 (47.5) 3117 (8.0) — 38 738 (99.9) 53 (0.1) — 
 ≥40 4092 (45.4) 4113 (45.6) 811 (9.0) — 9009 (99.9) 7 (0.1) — 
 Missing 6 (40.0) 1 (6.7) 8 (53.3) — 15 (100.0) 0 (0.0) — 
Maternal indigenous status    <.001   .47 
 Not indigenous 84 227 (46.2) 84 200 (46.2) 13 813 (7.6) — 182 069 (99.9) 171 (0.1) — 
 Indigenous 1483 (56.9) 1003 (38.5) 120 (4.6) — 2602 (99.8) 4 (0.2) — 
 Unknown 302 (54.1) 162 (29.0) 94 (16.8) — 558 (100.0) 0 (0.0) — 
Country of birth    <.001   .27 
 Australian born 53 492 (46.8) 53 745 (47.0) 7065 (6.2) — 114 185 (99.9) 117 (0.1) — 
 Born overseas 32 120 (45.7) 31 326 (44.6) 6840 (9.7) — 70 228 (99.9) 58 (0.1) — 
 Missing 400 (49.0) 294 (36.0) 122 (15.0) — 816 (100.0) 0 (0.0) — 
Smoked at any time during pregnancy    <.001   .31 
 Did not smoke 73 070 (45.3) 75 601 (46.9) 12 502 (7.8) — 161 021 (99.9) 152 (0.1) — 
 Smoked 9346 (57.5) 5903 (36.3) 1008 (6.2) — 16 245 (99.9) 12 (0.1) — 
 Missing 3596 (45.1) 3861 (48.4) 517 (6.5) — 7963 (99.9) 11 (0.1) — 
Parity    <.001   <.001 
 Multiparas 51 875 (49.7) 44 567 (42.7) 8000 (7.7) — 104 306 (99.9) 136 (0.1) — 
 Primiparas 34 137 (42.2) 40 798 (50.4) 6027 (7.4) — 80 923 (100.0) 39 (0.0) — 
Plurality    <.001   .92 
 Singleton 83 681 (46.4) 83 170 (46.1) 13 498 (7.5) — 180 178 (99.9) 171 (0.1) — 
 Multiple birth 2300 (46.0) 2195 (43.9) 502 (10.0) — 4993 (99.9) 4 (0.1) — 
 Missing 31 (53.4) 0 (0.0) 27 (46.6) — 58 (100.0) 0 (0.0) — 
Discipline of antenatal care provider    <.001   .017 
 No antenatal care provider 388 (78.9) 51 (10.4) 53 (10.8) — 492 (100.0) 0 (0.0) — 
 General practitioner 9798 (42.4) 12 494 (54.1) 822 (3.6) — 23 099 (99.9) 15 (0.1) — 
 Midwife 28 698 (48.2) 26 105 (43.8) 4743 (8.0) — 59 504 (99.9) 42 (0.1) — 
 Obstetrician 46 657 (46.0) 46 355 (45.7) 8350 (8.2) — 101 246 (99.9) 116 (0.1) — 
 Missing 471 (52.9) 360 (40.4) 59 (6.6) — 888 (99.8) 2 (0.2) — 
Gestational age at first antenatal visit    <.001   .23 
 ≥24 wk 6263 (55.9) 3918 (35.0) 1025 (9.1) — 11 201 (100.0) 5 (0.0) — 
 12–23 wk 40 795 (48.3) 37 051 (43.8) 6687 (7.9) — 84 457 (99.9) 76 (0.1) — 
 ≤11 wk 38 107 (43.2) 43 985 (49.9) 6057 (6.9) — 88 057 (99.9) 92 (0.1) — 
 Missing 847 (55.9) 411 (27.1) 258 (17.0) — 1514 (99.9) 2 (0.1) — 
Gestational age at birth, wk    <.001   .079 
 <28 471 (63.9) 155 (21.0) 111 (15.1) — 736 (99.9) 1 (0.1) — 
 28–36 6770 (48.2) 5896 (42.0) 1367 (9.7) — 14 012 (99.9) 21 (0.1) — 
 ≥37 78 771 (46.2) 79 314 (46.5) 12 549 (7.4) — 170 481 (99.9) 153 (0.1) — 
Any preexisting maternal medical conditiona 1276 (1.5) 1401 (1.6) 278 (2.0) <.001 2951 (1.6) 4 (2.3) .46 
Any obstetric complicationb 22 584 (26.3) 21 728 (25.5) 2839 (20.2) <.001 47 110 (25.4) 41 (23.4) .54 
Maternal admission to HDU or ICU    <.001   .81 
 Not admitted 84 459 (46.4) 84 025 (46.1) 13 693 (7.5) — 182 004 (99.9) 173 (0.1) — 
 Admitted 1504 (48.9) 1298 (42.2) 275 (8.9) — 3075 (99.9) 2 (0.1) — 
 Missing 49 (32.7) 42 (28.0) 59 (39.3) — 150 (100.0) 0 (0.0) — 
Apgar score at 5 min    <.001   .83 
 0–3 331 (56.2) 183 (31.1) 75 (12.7) — 589 (100.0) 0 (0.0) — 
 4–6 1401 (47.7) 1285 (43.8) 249 (8.5) — 2932 (99.9) 3 (0.1) — 
 ≥7 84 102 (46.3) 83 795 (46.1) 13 674 (7.5) — 181 399 (99.9) 172 (0.1) — 
 Missing 178 (57.6) 102 (33.0) 29 (9.4) — 309 (100.0) 0 (0.0) — 
Birth wt, g    <.001   .029 
 <1500 1011 (57.0) 494 (27.8) 269 (15.2) — 1769 (99.7) 5 (0.3) — 
 1500–<2500 5008 (49.1) 4259 (41.7) 937 (9.2) — 10 190 (99.9) 14 (0.1) — 
 ≥2500 79 965 (46.1) 80 597 (46.5) 12 806 (7.4) — 173 212 (99.9) 156 (0.1) — 
 Missing 28 (48.3) 15 (25.9) 15 (25.9) — 58 (100.0) 0 (0.0) — 
Infant admission to SCN or ICU    <.001   .024 
 Not admitted 69 014 (46.2) 69 208 (46.3) 11 112 (7.4) — 149 202 (99.9) 132 (0.1) — 
 Admitted 14 708 (47.1) 13 724 (43.9) 2797 (9.0) — 31 196 (99.9) 33 (0.1) — 
 Missing 2290 (47.3) 2433 (50.3) 118 (2.4) — 4831 (99.8) 10 (0.2) — 
Infant feeding in hospital    <.001   .68 
 Exclusively breastfed 29 509 (47.3) 27 791 (44.6) 5076 (8.1) — 62 313 (99.9) 63 (0.1) — 
 Nonexclusively breastfed 54 960 (45.9) 56 365 (47.1) 8429 (7.0) — 119 646 (99.9) 108 (0.1) — 
 Missing 1543 (47.1) 1209 (36.9) 522 (15.9) — 3270 (99.9) 4 (0.1) — 
Infant quarter of birth    <.001   <.001 
 January to March 24 679 (61.8) 11 738 (29.4) 3513 (8.8) — 39 882 (99.9) 48 (0.1) — 
 April to June 20 651 (52.4) 15 691 (39.8) 3081 (7.8) — 39 355 (99.8) 68 (0.2) — 
 July to September 16 688 (35.6) 26 992 (57.6) 3174 (6.8) — 46 809 (99.9) 45 (0.1) — 
 October to December 23 994 (40.5) 30 944 (52.3) 4259 (7.2) — 59 183 (100.0) 14 (0.0) — 

HDU, high dependency unit; SCN, special care nursery; —, not applicable.

a

Any preexisting maternal medical condition, including preexisting essential hypertension complicating pregnancy, childbirth and the puerperium, preexisting type 1 or type 2 diabetes, diseases of the circulatory system complicating pregnancy, childbirth and the puerperium.

b

Any obstetric complication includes pre-eclampsia and hemolysis, elevated liver enzymes, low platelet count syndrome, Antepartum hemorrhage, gestational diabetes arising at or after 24 wk gestation (diet controlled or insulin treated), suspected fetal growth restriction, carrier of Streptococcus group B.

TABLE 2

Characteristics of Cohort by Maternal Vaccination Status and Laboratory-Confirmed Pertussis Notification in Infants (<6 mo; N = 184 194)

Maternal Pertussis Vaccination StatusInfant Pertussis Notification
Not Vaccinated (n = 41 518), n (%)Vaccinated (n =127 026), n (%)Missing (n = 15 650), n (%)PNo (n = 184 143), n (%)Yes (n = 51), n (%)P
Vaccinated this pregnancy against Pertussis       <.001 
 Not vaccinated — — — — 41 494 (99.9) 24 (0.1) — 
 Vaccinated — — — — 126 999 (100.0) 27 (0.0) — 
 Missing or unknown — — — — 15 650 (100.0) 0 (0.0) — 
Maternal age, y    <.001   .22 
 <18 160 (27.2) 384 (65.2) 45 (7.6) — 589 (100.0) 0 (0.0) — 
 18–24 4782 (25.1) 13 039 (68.4) 1232 (6.5) — 19 043 (99.9) 10 (0.1) — 
 25–29 10 268 (21.8) 33 563 (71.1) 3343 (7.1) — 47 164 (100.0) 10 (0.0) — 
 30–34 14 885 (21.3) 48 798 (69.8) 6198 (8.9) — 69 865 (100.0) 16 (0.0) — 
 35–39 9185 (23.8) 25 532 (66.2) 3830 (9.9) — 38 537 (100.0) 10 (0.0) — 
 ≥40 2232 (25.0) 5709 (63.9) 994 (11.1) — 8930 (99.9) 5 (0.1) — 
 Missing 6 (40.0) 1 (6.7) 8 (53.3) — 15 (100.0) 0 (0.0) — 
Maternal indigenous status    <.001   .29 
 Not indigenous 40 578 (22.4) 125 050 (69.1) 15 443 (8.5) — 181 022 (100.0) 49 (0.0) — 
 Indigenous 793 (30.8) 1666 (64.7) 116 (4.5) — 2573 (99.9) 2 (0.1) — 
 Unknown 147 (26.8) 310 (56.6) 91 (16.6) — 548 (100.0) 0 (0.0) — 
Country of birth    <.001   .88 
 Australian born 23 423 (20.6) 81 695 (72.0) 8423 (7.4) — 113 510 (100.0) 31 (0.0) — 
 Born overseas 17 843 (25.5) 44 889 (64.3) 7109 (10.2) — 69 821 (100.0) 20 (0.0) — 
 Missing 252 (31.0) 442 (54.4) 118 (14.5) — 812 (100.0) 0 (0.0) — 
Smoked at any time during pregnancy    <.001   .45 
 Did not smoke 35 030 (21.9) 111 030 (69.3) 14 131 (8.8) — 160 149 (100.0) 42 (0.0) — 
 Smoked 4510 (28.0) 10 565 (65.7) 1005 (6.3) — 16 073 (100.0) 7 (0.0) — 
 Missing 1978 (25.0) 5431 (68.5) 514 (6.5) — 7921 (100.0) 2 (0.0) — 
Parity    <.001   <.001 
 Multiparas 27 661 (26.6) 67 337 (64.8) 8894 (8.6) — 103 850 (100.0) 42 (0.0) — 
 Primiparas 13 857 (17.3) 59 689 (74.3) 6756 (8.4) — 80 293 (100.0) 9 (0.0) — 
Plurality    <.001   .96 
 Singleton 40 296 (22.5) 124 116 (69.2) 15 060 (8.4) — 179 422 (100.0) 50 (0.0) — 
 Multiple birth 1192 (25.6) 2909 (62.4) 563 (12.1) — 4663 (100.0) 1 (0.0) — 
 Missing 30 (51.7) 1 (1.7) 27 (46.6) — 58 (100.0) 0 (0.0) — 
Discipline of antenatal care provider    <.001   .23 
 No antenatal care provider 292 (61.5) 123 (25.9) 60 (12.6) — 475 (100.0) 0 (0.0) — 
 General practitioner 3499 (15.2) 18 840 (81.7) 723 (3.1) — 23 057 (100.0) 5 (0.0) — 
 Midwife 13 602 (22.9) 41 480 (69.8) 4324 (7.3) — 59 396 (100.0) 10 (0.0) — 
 Obstetrician 23 881 (23.8) 66 019 (65.8) 10 488 (10.4) — 100 352 (100.0) 36 (0.0) — 
 Missing 244 (28.3) 564 (65.4) 55 (6.4) — 863 (100.0) 0 (0.0) — 
Gestational age at first antenatal visit, wk    <.001   .44 
 ≥24 3593 (32.6) 6450 (58.5) 983 (8.9) — 11 021 (100.0) 5 (0.0) — 
 12–23 19 439 (23.1) 58 308 (69.4) 6257 (7.4) — 83 985 (100.0) 19 (0.0) — 
 ≤11 17 929 (20.4) 61 647 (70.3) 8153 (9.3) — 87 702 (100.0) 27 (0.0) — 
 Missing 557 (38.8) 621 (43.3) 257 (17.9) — 1435 (100.0) 0 (0.0) — 
Gestational age at birth, wk    <.001   .005 
 30–36 3778 (27.9) 8325 (61.4) 1457 (10.7) — 13 551 (99.9) 9 (0.1) — 
 ≥37 37 740 (22.1) 118 701 (69.6) 14 193 (8.3) — 170 592 (100.0) 42 (0.0) — 
Any preexisting maternal medical condition 680 (1.6) 1894 (1.5) 313 (2.0) <.001 2886 (1.6) 1 (2.0) .82 
Any obstetric complication 10 505 (25.3) 33 119 (26.1) 3092 (19.8) <.001 46 703 (25.4) 13 (25.5) .98 
Maternal admission to HDU or ICU    <.001   .65 
 Not admitted 40 760 (22.5) 125 013 (69.0) 15 314 (8.5) — 181 036 (100.0) 51 (0.0) — 
 Admitted 732 (24.8) 1970 (66.6) 255 (8.6) — 2957 (100.0) 0 (0.0) — 
 Missing 26 (17.3) 43 (28.7) 81 (54.0) — 150 (100.0) 0 (0.0) — 
Apgar score at 5 min    <.001   .81 
 0–3 114 (31.1) 216 (59.0) 36 (9.8) — 366 (100.0) 0 (0.0) — 
 4–6 616 (22.8) 1862 (68.8) 227 (8.4) — 2705 (100.0) 0 (0.0) — 
 ≥7 40 687 (22.5) 124 787 (69.0) 15 366 (8.5) — 180 789 (100.0) 51 (0.0) — 
 Missing 101 (35.7) 161 (56.9) 21 (7.4) — 283 (100.0) 0 (0.0) — 
Birth wt, g    <.001   .98 
 <1500 206 (33.4) 316 (51.3) 94 (15.3) — 616 (100.0) 0 (0.0) — 
 1500–<2500 2789 (27.5) 6324 (62.3) 1042 (10.3) — 10 152 (100.0) 3 (0.0) — 
 ≥2500 38 500 (22.2) 120 368 (69.4) 14 499 (8.4) — 173 319 (100.0) 48 (0.0) — 
 Missing 23 (41.1) 18 (32.1) 15 (26.8) — 56 (100.0) 0 (0.0) — 
Infant admission to SCN or ICU    <.001   .80 
 Not admitted 33 308 (22.3) 103 135 (69.2) 12 696 (8.5) — 149 099 (100.0) 40 (0.0) — 
 Admitted 7171 (23.7) 20 213 (66.9) 2832 (9.4) — 30 206 (100.0) 10 (0.0) — 
 Missing 1039 (21.5) 3678 (76.0) 122 (2.5) — 4838 (100.0) 1 (0.0) — 
Infant feeding in hospital    <.001   .18 
 Exclusively breastfed 15 142 (24.4) 41 101 (66.2) 5883 (9.5) — 62 105 (100.0) 21 (0.0) — 
 Nonexclusively breastfed 25 629 (21.5) 84 237 (70.7) 9320 (7.8) — 119 158 (100.0) 28 (0.0) — 
 Missing 747 (25.9) 1688 (58.6) 447 (15.5) — 2880 (99.9) 2 (0.1) — 
Infant birth cohort    <.001   .32 
 September 2015 to December 2015 8764 (33.0) 14 685 (55.3) 3109 (11.7) — 26 546 (100.0) 12 (0.0) — 
 January 2016 to April 2016 7733 (29.0) 15 761 (59.1) 3162 (11.9) — 26 652 (100.0) 4 (0.0) — 
 May 2016 to August 2016 5948 (22.4) 17 723 (66.8) 2875 (10.8) — 26 539 (100.0) 7 (0.0) — 
 September 2016 to December 2016 5683 (21.7) 17 885 (68.4) 2585 (9.9) — 26 143 (100.0) 10 (0.0) — 
 January 2017 to April 2017 5097 (19.7) 19 104 (73.9) 1646 (6.4) — 25 840 (100.0) 7 (0.0) — 
 May 2017 to August 2017 4142 (15.8) 20 854 (79.4) 1254 (4.8) — 26 243 (100.0) 7 (0.0) — 
 September 2017 to December 2017 4151 (15.9) 21 014 (80.3) 1019 (3.9) — 26 180 (100.0) 4 (0.0) — 
Maternal Pertussis Vaccination StatusInfant Pertussis Notification
Not Vaccinated (n = 41 518), n (%)Vaccinated (n =127 026), n (%)Missing (n = 15 650), n (%)PNo (n = 184 143), n (%)Yes (n = 51), n (%)P
Vaccinated this pregnancy against Pertussis       <.001 
 Not vaccinated — — — — 41 494 (99.9) 24 (0.1) — 
 Vaccinated — — — — 126 999 (100.0) 27 (0.0) — 
 Missing or unknown — — — — 15 650 (100.0) 0 (0.0) — 
Maternal age, y    <.001   .22 
 <18 160 (27.2) 384 (65.2) 45 (7.6) — 589 (100.0) 0 (0.0) — 
 18–24 4782 (25.1) 13 039 (68.4) 1232 (6.5) — 19 043 (99.9) 10 (0.1) — 
 25–29 10 268 (21.8) 33 563 (71.1) 3343 (7.1) — 47 164 (100.0) 10 (0.0) — 
 30–34 14 885 (21.3) 48 798 (69.8) 6198 (8.9) — 69 865 (100.0) 16 (0.0) — 
 35–39 9185 (23.8) 25 532 (66.2) 3830 (9.9) — 38 537 (100.0) 10 (0.0) — 
 ≥40 2232 (25.0) 5709 (63.9) 994 (11.1) — 8930 (99.9) 5 (0.1) — 
 Missing 6 (40.0) 1 (6.7) 8 (53.3) — 15 (100.0) 0 (0.0) — 
Maternal indigenous status    <.001   .29 
 Not indigenous 40 578 (22.4) 125 050 (69.1) 15 443 (8.5) — 181 022 (100.0) 49 (0.0) — 
 Indigenous 793 (30.8) 1666 (64.7) 116 (4.5) — 2573 (99.9) 2 (0.1) — 
 Unknown 147 (26.8) 310 (56.6) 91 (16.6) — 548 (100.0) 0 (0.0) — 
Country of birth    <.001   .88 
 Australian born 23 423 (20.6) 81 695 (72.0) 8423 (7.4) — 113 510 (100.0) 31 (0.0) — 
 Born overseas 17 843 (25.5) 44 889 (64.3) 7109 (10.2) — 69 821 (100.0) 20 (0.0) — 
 Missing 252 (31.0) 442 (54.4) 118 (14.5) — 812 (100.0) 0 (0.0) — 
Smoked at any time during pregnancy    <.001   .45 
 Did not smoke 35 030 (21.9) 111 030 (69.3) 14 131 (8.8) — 160 149 (100.0) 42 (0.0) — 
 Smoked 4510 (28.0) 10 565 (65.7) 1005 (6.3) — 16 073 (100.0) 7 (0.0) — 
 Missing 1978 (25.0) 5431 (68.5) 514 (6.5) — 7921 (100.0) 2 (0.0) — 
Parity    <.001   <.001 
 Multiparas 27 661 (26.6) 67 337 (64.8) 8894 (8.6) — 103 850 (100.0) 42 (0.0) — 
 Primiparas 13 857 (17.3) 59 689 (74.3) 6756 (8.4) — 80 293 (100.0) 9 (0.0) — 
Plurality    <.001   .96 
 Singleton 40 296 (22.5) 124 116 (69.2) 15 060 (8.4) — 179 422 (100.0) 50 (0.0) — 
 Multiple birth 1192 (25.6) 2909 (62.4) 563 (12.1) — 4663 (100.0) 1 (0.0) — 
 Missing 30 (51.7) 1 (1.7) 27 (46.6) — 58 (100.0) 0 (0.0) — 
Discipline of antenatal care provider    <.001   .23 
 No antenatal care provider 292 (61.5) 123 (25.9) 60 (12.6) — 475 (100.0) 0 (0.0) — 
 General practitioner 3499 (15.2) 18 840 (81.7) 723 (3.1) — 23 057 (100.0) 5 (0.0) — 
 Midwife 13 602 (22.9) 41 480 (69.8) 4324 (7.3) — 59 396 (100.0) 10 (0.0) — 
 Obstetrician 23 881 (23.8) 66 019 (65.8) 10 488 (10.4) — 100 352 (100.0) 36 (0.0) — 
 Missing 244 (28.3) 564 (65.4) 55 (6.4) — 863 (100.0) 0 (0.0) — 
Gestational age at first antenatal visit, wk    <.001   .44 
 ≥24 3593 (32.6) 6450 (58.5) 983 (8.9) — 11 021 (100.0) 5 (0.0) — 
 12–23 19 439 (23.1) 58 308 (69.4) 6257 (7.4) — 83 985 (100.0) 19 (0.0) — 
 ≤11 17 929 (20.4) 61 647 (70.3) 8153 (9.3) — 87 702 (100.0) 27 (0.0) — 
 Missing 557 (38.8) 621 (43.3) 257 (17.9) — 1435 (100.0) 0 (0.0) — 
Gestational age at birth, wk    <.001   .005 
 30–36 3778 (27.9) 8325 (61.4) 1457 (10.7) — 13 551 (99.9) 9 (0.1) — 
 ≥37 37 740 (22.1) 118 701 (69.6) 14 193 (8.3) — 170 592 (100.0) 42 (0.0) — 
Any preexisting maternal medical condition 680 (1.6) 1894 (1.5) 313 (2.0) <.001 2886 (1.6) 1 (2.0) .82 
Any obstetric complication 10 505 (25.3) 33 119 (26.1) 3092 (19.8) <.001 46 703 (25.4) 13 (25.5) .98 
Maternal admission to HDU or ICU    <.001   .65 
 Not admitted 40 760 (22.5) 125 013 (69.0) 15 314 (8.5) — 181 036 (100.0) 51 (0.0) — 
 Admitted 732 (24.8) 1970 (66.6) 255 (8.6) — 2957 (100.0) 0 (0.0) — 
 Missing 26 (17.3) 43 (28.7) 81 (54.0) — 150 (100.0) 0 (0.0) — 
Apgar score at 5 min    <.001   .81 
 0–3 114 (31.1) 216 (59.0) 36 (9.8) — 366 (100.0) 0 (0.0) — 
 4–6 616 (22.8) 1862 (68.8) 227 (8.4) — 2705 (100.0) 0 (0.0) — 
 ≥7 40 687 (22.5) 124 787 (69.0) 15 366 (8.5) — 180 789 (100.0) 51 (0.0) — 
 Missing 101 (35.7) 161 (56.9) 21 (7.4) — 283 (100.0) 0 (0.0) — 
Birth wt, g    <.001   .98 
 <1500 206 (33.4) 316 (51.3) 94 (15.3) — 616 (100.0) 0 (0.0) — 
 1500–<2500 2789 (27.5) 6324 (62.3) 1042 (10.3) — 10 152 (100.0) 3 (0.0) — 
 ≥2500 38 500 (22.2) 120 368 (69.4) 14 499 (8.4) — 173 319 (100.0) 48 (0.0) — 
 Missing 23 (41.1) 18 (32.1) 15 (26.8) — 56 (100.0) 0 (0.0) — 
Infant admission to SCN or ICU    <.001   .80 
 Not admitted 33 308 (22.3) 103 135 (69.2) 12 696 (8.5) — 149 099 (100.0) 40 (0.0) — 
 Admitted 7171 (23.7) 20 213 (66.9) 2832 (9.4) — 30 206 (100.0) 10 (0.0) — 
 Missing 1039 (21.5) 3678 (76.0) 122 (2.5) — 4838 (100.0) 1 (0.0) — 
Infant feeding in hospital    <.001   .18 
 Exclusively breastfed 15 142 (24.4) 41 101 (66.2) 5883 (9.5) — 62 105 (100.0) 21 (0.0) — 
 Nonexclusively breastfed 25 629 (21.5) 84 237 (70.7) 9320 (7.8) — 119 158 (100.0) 28 (0.0) — 
 Missing 747 (25.9) 1688 (58.6) 447 (15.5) — 2880 (99.9) 2 (0.1) — 
Infant birth cohort    <.001   .32 
 September 2015 to December 2015 8764 (33.0) 14 685 (55.3) 3109 (11.7) — 26 546 (100.0) 12 (0.0) — 
 January 2016 to April 2016 7733 (29.0) 15 761 (59.1) 3162 (11.9) — 26 652 (100.0) 4 (0.0) — 
 May 2016 to August 2016 5948 (22.4) 17 723 (66.8) 2875 (10.8) — 26 539 (100.0) 7 (0.0) — 
 September 2016 to December 2016 5683 (21.7) 17 885 (68.4) 2585 (9.9) — 26 143 (100.0) 10 (0.0) — 
 January 2017 to April 2017 5097 (19.7) 19 104 (73.9) 1646 (6.4) — 25 840 (100.0) 7 (0.0) — 
 May 2017 to August 2017 4142 (15.8) 20 854 (79.4) 1254 (4.8) — 26 243 (100.0) 7 (0.0) — 
 September 2017 to December 2017 4151 (15.9) 21 014 (80.3) 1019 (3.9) — 26 180 (100.0) 4 (0.0) — 

HDU, high dependency unit; SCN, special care nursery; —, not applicable.

The record-linkage process identified 241 infants having any one of the influenza-specific outcomes of interest: 175 (94.4 per 100 000) with a laboratory-confirmed influenza notification, 25 (13.5 per 100 000) with an ED presentation, and 111 (59.9 per 100 000) with a hospitalization. No infants were identified as having died (Fig 2A). Most influenza events occurred in 2017, with a peak observed between June and October each year (data are not shown). For pertussis, 116 infants were identified as having any one of the pertussis-specific outcomes of interest, including 51 (27.7 per 100 000) with a laboratory-confirmed pertussis notification and 1 death (0.5 per 100 000), 59 (32.0 per 100 000) with an ED presentation, and 39 (21.2 per 100 000) with a hospitalization (Fig 2B). The number of pertussis events ranged from 0 to 8 events per month (data are not shown).

FIGURE 2

A, Influenza outcomes (infants <6 months). Birth cohort = 185 404. B, Pertussis outcomes (infants <6 months; n = 116). Birth cohort = 184 894. Figures generated using Larsson J (2020). eulerr: Area-Proportional Euler and Venn Diagrams with Ellipses. R package version 6.1.0, https://cran.r-project.org/package=eulerr. Accessed May 31, 2019.

FIGURE 2

A, Influenza outcomes (infants <6 months). Birth cohort = 185 404. B, Pertussis outcomes (infants <6 months; n = 116). Birth cohort = 184 894. Figures generated using Larsson J (2020). eulerr: Area-Proportional Euler and Venn Diagrams with Ellipses. R package version 6.1.0, https://cran.r-project.org/package=eulerr. Accessed May 31, 2019.

Close modal

Compared with infants born to women who were not vaccinated against influenza during pregnancy, the risk of having a laboratory-confirmed influenza notification among infants (aged <2 months) born to women who were vaccinated was reduced (aRR: 0.44 [95% CI, 0.25% to 0.77%; P < .004]; VE: 56.1% [95% CI, 23.3% to 74.9%]). This protective effect was retained, albeit attenuated, among older infants aged 2 to <6 months (aRR: 0.64 [95% CI, 0.42% to 0.98%; P < .039]; VE: 35.7% [95% CI, 2.2% to 57.7%]). The risk of influenza was also reduced for all secondary outcomes: Any influenza event among infants aged <2 months born to vaccinated women was reduced compared with those born to unvaccinated women (aRR: 0.63 [95% CI, 0.40% to 0.98%; P = .039]; VE: 37.2% [95% CI, 2.3% to 59.7%]), and the risk of being hospitalized because of laboratory-confirmed influenza or influenzalike infection was reduced by 34% (aRR: 0.66 [95% CI, 0.38% to 1.15%; P < .140]; VE: 34.4% [95% CI −14.8% to 62.5%]; Table 3). A sensitivity analysis was conducted to assess the effectiveness of the influenza vaccine in 2016 and 2017 as separate seasons. Using laboratory-confirmed notified influenza infection in infants (aged <6 months) as the main outcome measure, we observed a higher VE in 2016 (VE: 61.2% [95% CI, 21.9% to 80.8%]) than 2017 (VE: 52.3% [95% CI, 26.9% to 68.8%]; data are not shown). On the basis of an overall VE of 44.8% among infants aged <6 months, complete vaccination would have resulted in 22 (12.8%) fewer notified influenza cases in infants over the study period.

TABLE 3

Unadjusted Risk Ratios and aRRs, 95% CIs, and Influenza VE Estimates Among Infants Born to Vaccinated Mothers

Cases, n (%)RR (95% CI)aRR (95% CI)aVE (95% CI)
Influenza notification     
 <2 mo     
  Not vaccinated 42 (0.1) Reference Reference Reference 
  Vaccinated 20 (0.0) 0.48 (0.28 to 0.82) 0.44 (0.25 to 0.77) 56.10 (23.31 to 74.87) 
  Missing 2 (0.0) 0.29 (0.07 to 1.21) 0.29 (0.07 to 1.21) 70.87 (−20.61 to 92.96) 
 2–<6 mo     
  Not vaccinated 69 (0.1) Reference Reference Reference 
  Vaccinated 30 (0.0) 0.46 (0.30 to 0.70) 0.64 (0.42 to 0.98) 35.70 (2.19 to 57.73) 
  Missing 12 (0.1) 1.08 (0.59 to 2.00) 1.16 (0.63 to 2.14) −16.07 (−114.41 to 37.17) 
 <6 mo     
  Not vaccinated 111 (0.1) Reference Reference Reference 
  Vaccinated 50 (0.1) 0.47 (0.34 to 0.65) 0.55 (0.39 to 0.78) 44.79 (22.32 to 60.76) 
  Missing 14 (0.1) 0.78 (0.45 to 1.36) 0.81 (0.46 to 1.43) 18.59 (−42.55 to 53.51) 
Any influenza outcome     
 <2 mo     
  Not vaccinated 53 (0.1) Reference Reference Reference 
  Vaccinated 36 (0.0) 0.68 (0.45 to 1.05) 0.63 (0.40 to 0.98) 37.24 (2.27 to 59.70) 
  Missing 5 (0.0) 0.58 (0.23 to 1.45) 0.57 (0.23 to 1.43) 42.73 (−43.17 to 77.09) 
 2–<6 mo     
  Not vaccinated 90 (0.1) Reference Reference Reference 
  Vaccinated 44 (0.1) 0.51 (0.36 to 0.73) 0.71 (0.50 to 1.01) 28.99 (−1.48 to 50.31) 
  Missing 13 (0.1) 0.90 (0.50 to 1.60) 0.94 (0.52 to 1.68) 6.43 (−68.47 to 48.02) 
 <6 mo     
  Not vaccinated 143 (0.2) Reference Reference Reference 
  Vaccinated 80 (0.1) 0.57 (0.44 to 0.76) 0.68 (0.51 to 0.89) 32.46 (10.66 to 48.94) 
  Missing 18 (0.1) 0.78 (0.48 to 1.27) 0.80 (0.49 to 1.30) 20.42 (−30.41 to 51.43) 
Severe influenza     
 <2 mo     
  Not vaccinated 31 (0.0) Reference Reference Reference 
  Vaccinated 22 (0.0) 0.72 (0.41 to 1.23) 0.66 (0.38 to 1.15) 34.37 (−14.83 to 62.49) 
  Missing 3 (0.0) 0.59 (0.18 to 1.94) 0.56 (0.17 to 1.84) 43.62 (−84.39 to 82.76) 
 2–<6 mo     
  Not vaccinated 30 (0.0) Reference Reference Reference 
  Vaccinated 20 (0.0) 0.73 (0.42 to 1.28) 0.96 (0.55 to 1.67) 4.00 (−66.75 to 44.73) 
  Missing 5 (0.0) 1.06 (0.41 to 2.73) 1.03 (0.39 to 2.72) −3.01 (−172.03 to 60.99) 
 <6 mo     
  Not vaccinated 61 (0.1) Reference Reference Reference 
  Vaccinated 42 (0.1) 0.72 (0.49 to 1.07) 0.79 (0.53 to 1.18) 20.85 (−17.74 to 46.79) 
  Missing 8 (0.1) 0.82 (0.39 to 1.71) 0.79 (0.37 to 1.66) 21.01 (−66.42 to 62.51) 
Cases, n (%)RR (95% CI)aRR (95% CI)aVE (95% CI)
Influenza notification     
 <2 mo     
  Not vaccinated 42 (0.1) Reference Reference Reference 
  Vaccinated 20 (0.0) 0.48 (0.28 to 0.82) 0.44 (0.25 to 0.77) 56.10 (23.31 to 74.87) 
  Missing 2 (0.0) 0.29 (0.07 to 1.21) 0.29 (0.07 to 1.21) 70.87 (−20.61 to 92.96) 
 2–<6 mo     
  Not vaccinated 69 (0.1) Reference Reference Reference 
  Vaccinated 30 (0.0) 0.46 (0.30 to 0.70) 0.64 (0.42 to 0.98) 35.70 (2.19 to 57.73) 
  Missing 12 (0.1) 1.08 (0.59 to 2.00) 1.16 (0.63 to 2.14) −16.07 (−114.41 to 37.17) 
 <6 mo     
  Not vaccinated 111 (0.1) Reference Reference Reference 
  Vaccinated 50 (0.1) 0.47 (0.34 to 0.65) 0.55 (0.39 to 0.78) 44.79 (22.32 to 60.76) 
  Missing 14 (0.1) 0.78 (0.45 to 1.36) 0.81 (0.46 to 1.43) 18.59 (−42.55 to 53.51) 
Any influenza outcome     
 <2 mo     
  Not vaccinated 53 (0.1) Reference Reference Reference 
  Vaccinated 36 (0.0) 0.68 (0.45 to 1.05) 0.63 (0.40 to 0.98) 37.24 (2.27 to 59.70) 
  Missing 5 (0.0) 0.58 (0.23 to 1.45) 0.57 (0.23 to 1.43) 42.73 (−43.17 to 77.09) 
 2–<6 mo     
  Not vaccinated 90 (0.1) Reference Reference Reference 
  Vaccinated 44 (0.1) 0.51 (0.36 to 0.73) 0.71 (0.50 to 1.01) 28.99 (−1.48 to 50.31) 
  Missing 13 (0.1) 0.90 (0.50 to 1.60) 0.94 (0.52 to 1.68) 6.43 (−68.47 to 48.02) 
 <6 mo     
  Not vaccinated 143 (0.2) Reference Reference Reference 
  Vaccinated 80 (0.1) 0.57 (0.44 to 0.76) 0.68 (0.51 to 0.89) 32.46 (10.66 to 48.94) 
  Missing 18 (0.1) 0.78 (0.48 to 1.27) 0.80 (0.49 to 1.30) 20.42 (−30.41 to 51.43) 
Severe influenza     
 <2 mo     
  Not vaccinated 31 (0.0) Reference Reference Reference 
  Vaccinated 22 (0.0) 0.72 (0.41 to 1.23) 0.66 (0.38 to 1.15) 34.37 (−14.83 to 62.49) 
  Missing 3 (0.0) 0.59 (0.18 to 1.94) 0.56 (0.17 to 1.84) 43.62 (−84.39 to 82.76) 
 2–<6 mo     
  Not vaccinated 30 (0.0) Reference Reference Reference 
  Vaccinated 20 (0.0) 0.73 (0.42 to 1.28) 0.96 (0.55 to 1.67) 4.00 (−66.75 to 44.73) 
  Missing 5 (0.0) 1.06 (0.41 to 2.73) 1.03 (0.39 to 2.72) −3.01 (−172.03 to 60.99) 
 <6 mo     
  Not vaccinated 61 (0.1) Reference Reference Reference 
  Vaccinated 42 (0.1) 0.72 (0.49 to 1.07) 0.79 (0.53 to 1.18) 20.85 (−17.74 to 46.79) 
  Missing 8 (0.1) 0.82 (0.39 to 1.71) 0.79 (0.37 to 1.66) 21.01 (−66.42 to 62.51) 

Reference indicates unvaccinated mothers. RR, risk ratio.

The risk of laboratory-confirmed notified pertussis infection among infants aged <2 months born to women who were vaccinated, compared with those born to women who were not, was reduced by 80.1% (aRR: 0.20 [95% CI, 0.06% to 0.63%; P < .006]). A moderately protective effect was also observed for other outcomes of interest among infants aged <2 months, including having any pertussis outcome (aRR: 0.53 [95% CI, 0.30% to 0.93%; P < .026]) and severe pertussis (aRR: 0.38 [95% CI, 0.16% to 0.94%; P < .036]; Table 4). On the basis of an overall VE of 52.5% among infants <6 months of age, complete maternal vaccination would have resulted in 13 (24.7%) fewer notified pertussis cases in infants over the study period.

TABLE 4

Unadjusted Risk Ratios and aRRs, 95% CIs, and Pertussis VE Estimates Among Infants Born to Vaccinated Mothers

Cases, n (%)RR (95% CI)aRR (95% CI)VE (95% CI)
Pertussis notification     
 <2 mo     
  Not vaccinated 10 (0.0) Reference Reference Reference 
  Vaccinated 5 (0.0) 0.16 (0.06 to 0.48) 0.20 (0.06 to 0.63) 80.12 (37.06 to 93.72) 
  Missing 0 (0.0) NC NC NC 
 2–<6 mo     
  Not vaccinated 14 (0.0) Reference Reference Reference 
  Vaccinated 22 (0.0) 0.51 (0.26 to 1.00) 0.68 (0.33 to 1.39) 31.82 (−39.13 to 66.59) 
  Missing 0 (0.0) NC NC NC 
 <6 mo     
  Not vaccinated 24 (0.1) Reference Reference Reference 
  Vaccinated 27 (0.0) 0.37 (0.21 to 0.64) 0.48 (0.26 to 0.86) 52.47 (14.45 to 73.59) 
  Missing 0 (0.0) NC NC NC 
Any pertussis outcome     
 <2 mo     
  Not vaccinated 20 (0.1) Reference Reference Reference 
  Vaccinated 26 (0.0) 0.42 (0.24 to 0.76) 0.53 (0.30 to 0.93) 47.42 (7.29 to 70.18) 
  Missing 1 (0.0) 0.13 (0.02 to 0.99) 0.13 (0.02 to 1.00) 86.75 (−0.46 to 98.25) 
 2–<6 mo     
  Not vaccinated 20 (0.1) Reference Reference Reference 
  Vaccinated 46 (0.0) 0.75 (0.44 to 1.27) 1.07 (0.63 to 1.83) −7.09 (−83.31 to 37.44) 
  Missing 3 (0.0) 0.40 (0.12 to 1.34) 0.44 (0.13 to 1.47) 55.59 (−46.65 to 86.55) 
 <6 mo     
  Not vaccinated 40 (0.1) Reference Reference Reference 
  Vaccinated 72 (0.1) 0.59 (0.40 to 0.87) 0.79 (0.54 to 1.17) 20.84 (−16.89 to 46.39) 
  Missing 4 (0.0) 0.27 (0.09 to 0.74) 0.28 (0.10 to 0.79) 71.64 (21.05 to 89.82) 
Severe pertussis     
 <2 mo     
  Not vaccinated 10 (0.0) Reference Reference Reference 
  Vaccinated 8 (0.0) 0.26 (0.10 to 0.66) 0.38 (0.16 to 0.94) 61.66 (6.00 to 84.36) 
  Missing 0 (0.0) NC NC NC 
 2–<6 mo     
  Not vaccinated 6 (0.0) Reference Reference Reference 
  Vaccinated 15 (0.0) 0.82 (0.32 to 2.11) 1.05 (0.43 to 2.55) −4.63 (−155.35 to 57.13) 
  Missing 0 (0.0) NC NC NC 
 <6 mo     
  Not vaccinated 16 (0.0) Reference Reference Reference 
  Vaccinated 23 (0.0) 0.47 (0.25 to 0.89) 0.64 (0.35 to 1.17) 36.48 (−16.62 to 65.40) 
  Missing 0 (0.0) NC NC NC 
Cases, n (%)RR (95% CI)aRR (95% CI)VE (95% CI)
Pertussis notification     
 <2 mo     
  Not vaccinated 10 (0.0) Reference Reference Reference 
  Vaccinated 5 (0.0) 0.16 (0.06 to 0.48) 0.20 (0.06 to 0.63) 80.12 (37.06 to 93.72) 
  Missing 0 (0.0) NC NC NC 
 2–<6 mo     
  Not vaccinated 14 (0.0) Reference Reference Reference 
  Vaccinated 22 (0.0) 0.51 (0.26 to 1.00) 0.68 (0.33 to 1.39) 31.82 (−39.13 to 66.59) 
  Missing 0 (0.0) NC NC NC 
 <6 mo     
  Not vaccinated 24 (0.1) Reference Reference Reference 
  Vaccinated 27 (0.0) 0.37 (0.21 to 0.64) 0.48 (0.26 to 0.86) 52.47 (14.45 to 73.59) 
  Missing 0 (0.0) NC NC NC 
Any pertussis outcome     
 <2 mo     
  Not vaccinated 20 (0.1) Reference Reference Reference 
  Vaccinated 26 (0.0) 0.42 (0.24 to 0.76) 0.53 (0.30 to 0.93) 47.42 (7.29 to 70.18) 
  Missing 1 (0.0) 0.13 (0.02 to 0.99) 0.13 (0.02 to 1.00) 86.75 (−0.46 to 98.25) 
 2–<6 mo     
  Not vaccinated 20 (0.1) Reference Reference Reference 
  Vaccinated 46 (0.0) 0.75 (0.44 to 1.27) 1.07 (0.63 to 1.83) −7.09 (−83.31 to 37.44) 
  Missing 3 (0.0) 0.40 (0.12 to 1.34) 0.44 (0.13 to 1.47) 55.59 (−46.65 to 86.55) 
 <6 mo     
  Not vaccinated 40 (0.1) Reference Reference Reference 
  Vaccinated 72 (0.1) 0.59 (0.40 to 0.87) 0.79 (0.54 to 1.17) 20.84 (−16.89 to 46.39) 
  Missing 4 (0.0) 0.27 (0.09 to 0.74) 0.28 (0.10 to 0.79) 71.64 (21.05 to 89.82) 
Severe pertussis     
 <2 mo     
  Not vaccinated 10 (0.0) Reference Reference Reference 
  Vaccinated 8 (0.0) 0.26 (0.10 to 0.66) 0.38 (0.16 to 0.94) 61.66 (6.00 to 84.36) 
  Missing 0 (0.0) NC NC NC 
 2–<6 mo     
  Not vaccinated 6 (0.0) Reference Reference Reference 
  Vaccinated 15 (0.0) 0.82 (0.32 to 2.11) 1.05 (0.43 to 2.55) −4.63 (−155.35 to 57.13) 
  Missing 0 (0.0) NC NC NC 
 <6 mo     
  Not vaccinated 16 (0.0) Reference Reference Reference 
  Vaccinated 23 (0.0) 0.47 (0.25 to 0.89) 0.64 (0.35 to 1.17) 36.48 (−16.62 to 65.40) 
  Missing 0 (0.0) NC NC NC 

Reference indicates unvaccinated mothers. NC, not calculable; RR, risk ratio.

Results from the Cox model indicated that infant pertussis vaccination modified the effect of maternal pertussis vaccination. Overall, we found a VE of 63% (95% CI, 36.29% to 78.79%), and this varied by infant vaccination status. In infants born to unvaccinated women (and after adjusting for confounding factors) we observed no protection after receipt of the first infant dose (VE: 1.96% [95% CI, −172.41% to 64.71%]) and some protection after the second dose (VE: 32.84% [95% CI, −233.29% to 86.47%]). VE was the highest among infants born to vaccinated women who had not received any doses of a pertussis-containing vaccine themselves (VE: 81.69% [95% CI, 52.60% to 92.93%]), compared with unvaccinated infants born to unvaccinated women, but this fell with receipt of subsequent infant doses (Table 5). The point estimates were lower among infants born to vaccinated women who had received 1 (VE: 25.71% [95% CI, 79.78% to 69.30%]) or 2 (VE: −0.95%, [95% CI, −192.31% to 65.14%]) doses of primary-course pertussis vaccine. When we examined the risk of pertussis among vaccinated infants (who had received 2 primary-course doses), infants born to vaccinated women had a higher risk of pertussis compared with unvaccinated women, although this difference was not significant (aRR 1.50 [95% CI, 0.32% to 7.00%]; Table 5).

TABLE 5

Risk Ratios of Laboratory-Confirmed Pertussis Notification in Infants <6 Months of Age and Adjusted VE Estimates

Mother VaccinatedInfant DosesCases (N = 51)Infant Time At Risk (N = 30 839 303), dRR (95% CI)VE
Unadjusted model      
 No N/A 24 7 595 409 Referencea Referencea 
 Yes N/A 27 23 200 000 0.37 (0.21 to 0.64) 63.24 (36.29 to 78.79) 
Adjusted modelb      
 No 16 4 611 333 Referencea Referencea 
 No 1 927 934 0.98 (0.35 to 2.72) 1.96 (−172.41 to 64.71) 
 No 1 056 142 0.67 (0.14 to 3.33) 32.84 (−233.29 to 86.47) 
 Yes 12 000 000 0.18 (0.07 to 0.47) 81.69 (52.60 to 92.93) 
 Yes 12 6 931 348 0.74 (0.31 to 1.80) 25.71 (−79.78 to 69.30) 
 Yes 4 292 249 1.01 (0.35 to 2.92) −0.95 (−192.31 to 65.14) 
 No 1 927 934 Referenced Referenced 
 Yes 12 6 931 348 0.76 (0.28 to 2.04) 24.23 (−104.47 to 71.92) 
 No 1 056 142 Referencec Referencec 
 Yes 4 292 249 1.50 (0.32 to 7.00) −50.31 (−600.33 to 67.74) 
Mother VaccinatedInfant DosesCases (N = 51)Infant Time At Risk (N = 30 839 303), dRR (95% CI)VE
Unadjusted model      
 No N/A 24 7 595 409 Referencea Referencea 
 Yes N/A 27 23 200 000 0.37 (0.21 to 0.64) 63.24 (36.29 to 78.79) 
Adjusted modelb      
 No 16 4 611 333 Referencea Referencea 
 No 1 927 934 0.98 (0.35 to 2.72) 1.96 (−172.41 to 64.71) 
 No 1 056 142 0.67 (0.14 to 3.33) 32.84 (−233.29 to 86.47) 
 Yes 12 000 000 0.18 (0.07 to 0.47) 81.69 (52.60 to 92.93) 
 Yes 12 6 931 348 0.74 (0.31 to 1.80) 25.71 (−79.78 to 69.30) 
 Yes 4 292 249 1.01 (0.35 to 2.92) −0.95 (−192.31 to 65.14) 
 No 1 927 934 Referenced Referenced 
 Yes 12 6 931 348 0.76 (0.28 to 2.04) 24.23 (−104.47 to 71.92) 
 No 1 056 142 Referencec Referencec 
 Yes 4 292 249 1.50 (0.32 to 7.00) −50.31 (−600.33 to 67.74) 

N/A, not applicable; RR, risk ratio.

a

Unvaccinated mothers as the reference group.

b

Adjusted for maternal Aboriginal and/or Torres Strait Islander status, country of birth, maternal smoking status, parity, multiple birth, discipline of antenatal care provider, gestational age at first antenatal visit, gestational age at birth, maternal medical condition, and birth month. The interaction term included between maternal vaccination status and number of infant pertussis-containing vaccine received (0, 1, or 2).

c

Vaccinated infants and unvaccinated mothers as reference.

d

Vaccinated infants (2 doses) and unvaccinated mothers and the reference group.

Vaccination during pregnancy is an important strategy to prevent influenza and pertussis in pregnant women and infants. In this population-wide, inception cohort study, we demonstrated moderate effectiveness of maternal influenza and high effectiveness of maternal pertussis vaccines in preventing these diseases in infants born in Victoria, Australia between 2015 and 2017. Maternal influenza vaccination reduced the risk of laboratory-confirmed notified influenza in infants aged <2 months by 56.1%, and maternal pertussis vaccination reduced the risk of laboratory-confirmed notified pertussis by 80.1%. This evidence further supports global efforts to increase influenza and pertussis vaccination coverage among pregnant women.

Our VE estimates against laboratory-confirmed notified influenza among infants <2 months (56.1%) and 2–6 months (35.7%) are consistent with a recent systematic review reporting a pooled VE estimate of 48% among infants in the first 6 months of life.22  We also examined how well the vaccine matched circulating influenza strains each season: a factor that is often overlooked in studies reporting pooled estimates of the effectiveness of maternal influenza vaccines.22  We found a higher VE in 2016 compared with 2017, a finding that accords with published VE estimates among the general population.33,34 

For pertussis, we found that maternal vaccination was associated with a significant reduction in laboratory-confirmed notified infant pertussis, and this was most notable in infants aged <2 months, with a VE of 80.1%. High and sustained VE estimates reaching or exceeding 90% have been reported in studies using screening8,35  and case control7  study designs in the United Kingdom.

The lowered protective effect of maternal vaccination we observed among older infants (aged 2 to <6 months) for both conditions is consistent with waning maternal antibody concentrations with age. For pertussis, there was some evidence of increasing protection among infants born to unvaccinated women after the infants’ second primary dose. There has been some concern that serological responses of infants may be blunted by maternal antibodies, but the clinical significance of this is not known.36  Our study suggests that the protective effect of infant vaccine may be attenuated by maternal vaccination; however, this finding is based on low case numbers and considerable statistical uncertainty, and we urge caution in interpreting this result. We reinforce that our study and other studies have consistently revealed that maternal vaccination is highly protective against pertussis in young infants at the greatest risk of severe disease.

For both conditions, we observed low to moderate VE estimates against outcomes that included ED presentations and hospitalizations. This may reflect the low specificity of coded records captured on administrative data sets. To address this, we conducted a sensitivity analysis using only laboratory-confirmed hospitalizations, and this improved VE estimates among infants aged <2 months for severe influenza requiring hospitalization and severe pertussis requiring hospitalization, although numbers were small and CI wide (Supplemental Table 11).

The use of a stable and large, population-wide surveillance system capturing 186 962 mother-infant pairs provided a robust platform from which to link infant outcomes. However, some limitations to this approach should be considered. First, the study may have been subject to misclassification bias relating to maternal vaccination status. This data item is routinely collected by midwives at or around the time of vaccination or birth. Midwives may source maternal vaccination status from preexisting medical records (captured at the time of vaccination or during antenatal care visits) or patient self-report. To our knowledge, there are no financial incentives for the vaccination status of pregnant women to be incorrectly captured on patient medical files, and as such, misclassification of this data item is likely to be low. However, self-reported vaccination status may be influenced by recall bias: systematic misascertainment of exposure (vaccination) status. Although plausible, we consider that recall bias was likely to be low because the period of recall was short (a <40-weeks average period of gestation). In addition, in previous studies, it has been suggested that concordance between self-reported maternal vaccination status and medical records is good for both influenza and pertussis vaccines.37,38  Second, because the timing of vaccination during pregnancy (relative to gestational age) was not captured in the data sets used, we were unable to examine any time-varying effect that maternal vaccination has on the protective effect afforded to infants. To that end, we were also unable to exclude mother-infant pairs from the analyses who may have received the vaccine within 2 weeks of birth. Accordingly, some infants born to women who were classified as “vaccinated” may not have had the opportunity to receive any maternally derived antibody. Third, because of the study design, all infant outcomes were identified passively through linkage to administrative and other surveillance data sets. As such, ascertainment may be incomplete. In addition, this may have been differential by exposure status. For example, infants born to vaccinated women may be less likely to manifest severe disease requiring medical care and diagnosis than infants born to unvaccinated women. Other limitations may include the possibility of unmeasured confounding and loss to follow-up among infants whose families have moved interstate. However, given that the assessment of infant outcomes was restricted to the first 6 months of life, we would not expect this issue to be particularly large.

The promotion of maternal pertussis vaccination (in Australia and internationally) is largely driven by the benefits this vaccine affords infants. As a corollary, uptake of the pertussis vaccine during pregnancy is good, exceeding 80% in Victoria11  and elsewhere.39  Conversely, uptake of the influenza vaccine during pregnancy is low to moderate,11  as is the uptake and effectiveness of these vaccines among general adult populations.34  Public health messaging for maternal influenza vaccination should leverage the success of the pertussis program by clearly articulating the benefits that maternal influenza vaccination has on infants, as revealed by this study. Reshaping the message in this manner may improve the acceptance of this vaccine among pregnant women and health care providers. Furthermore (and because of changes in the recommendations for the administration of maternal pertussis vaccine in Australia [from 28 weeks’ gestation to, now, 20 weeks’ gestation]), coadministration of both vaccines earlier in pregnancy may improve the uptake of the influenza vaccine and overcome logistic barriers in administering 2 antenatal vaccines at different gestational ages. Further studies are needed to identify the optimal timing of maternal vaccine administration and the effect of the interval between maternal vaccination and birth and elucidate effects of maternally derived antibodies on infants’ response to active vaccination.

Maternal influenza and pertussis vaccination provides good protection to infants in early life, when active vaccination of infants themselves is not feasible. The evidence of effectiveness derived from this inception cohort study should be used to bolster global public health messaging to pregnant women and their health care providers and support system-level modifications required for these vaccines to be provided as part of routine antenatal care.

We are grateful to the Consultative Council on Obstetric and Paediatric Morbidity and Mortality for providing access to the deidentified data analyzed in this study and for the assistance of the staff at the Consultative Councils Unit of Safer Care Victoria. The conclusions, findings, opinions, and views or recommendations expressed in this article are those of the authors and do not necessarily reflect those of Consultative Council on Obstetric and Paediatric Morbidity and Mortality. We gratefully acknowledge the assistance of the Centre for Victorian Data Linkage in data extraction, preparation, and linkage. We also thank Stephen Pellissier, Simon Crouch, Rosemary Morey, and Helen Pitcher of the Health Protection Branch of the State Government Department of Health for their valuable contributions to the planning of this study and for reviewing the study’s findings. Finally, we gratefully acknowledge the midwives and antenatal care providers who are working to deliver maternal vaccination programs to pregnant women in Victoria and for their work in collecting the data captured in the VPDC.

Ms Rowe conceptualized and designed the study, conducted all analyses, drafted the initial manuscript, and finalized the manuscript; Prof Nolan and Dr Perrett conceptualized and designed the study and contributed to the preparation of the manuscript; Ms Romero supported study coordination and data cleaning; Prof Leder, A/Prof Stephens, and Prof Cowie supervised the study design and preparation of the manuscript; Prof Cheng supervised the study design, analyses, and preparation of the manuscript and critically reviewed the results of all analyses; and all authors contributed to the intellectual content of the manuscript, approved the final manuscript as submitted, and agree to be accountable for all components of the work.

FUNDING: Supported by the Victoria State Government Department of Health in Australia as part of routine vaccine program evaluation. No funding was secured for this study, other than the payment of salaries to Ms Rowe and Ms Romero as part of their role in the surveillance of communicable diseases in Victoria, Australia.

     
  • AIR

    Australian Immunisation Register

  •  
  • aRR

    adjusted risk ratio

  •  
  • CI

    confidence interval

  •  
  • ED

    emergency department

  •  
  • PHESS

    Public Health Event Surveillance System

  •  
  • VAED

    Victorian Admitted Episodes Dataset

  •  
  • VDI

    Victorian Death Index

  •  
  • VE

    vaccine effectiveness

  •  
  • VEMD

    Victorian Emergency Minimum Dataset

  •  
  • VPDC

    Victorian Perinatal Data Collection

1
World Health Organization
.
Vaccines against influenza WHO position paper – November 2012
.
Wkly Epidemiol Rec
.
2012
;
87
(
47
):
461
476
2
World Health Organization
.
Pertussis vaccines: WHO position paper - September 2015
.
Wkly Epidemiol Rec
.
2015
;
90
(
35
):
433
458
3
Romanin
V
,
Acosta
AM
,
Juarez
MDV
, et al
.
Maternal vaccination in Argentina: tetanus, diphtheria, and acellular pertussis vaccine effectiveness during pregnancy in preventing pertussis in infants <2 months of age
.
Clin Infect Dis
.
2020
;
70
(
3
):
380
387
4
Mølgaard-Nielsen
D
,
Fischer
TK
,
Krause
TG
,
Hviid
A
.
Effectiveness of maternal immunization with trivalent inactivated influenza vaccine in pregnant women and their infants
.
J Intern Med
.
2019
;
286
(
4
):
469
480
5
Galvao
TF
,
Silva
MT
,
Zimmermann
IR
,
Lopes
LAB
,
Bernardo
EF
,
Pereira
MG
.
Influenza vaccination in pregnant women: a systematic review
.
ISRN Prev Med
.
2013
;
2013
:
879493
6
Shakib
JH
,
Korgenski
K
,
Presson
AP
, et al
.
Influenza in infants born to women vaccinated during pregnancy
.
Pediatrics
.
2016
;
137
(
6
):
e20152360
7
Dabrera
G
,
Amirthalingam
G
,
Andrews
N
, et al
.
A case-control study to estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and Wales, 2012-2013
.
Clin Infect Dis
.
2015
;
60
(
3
):
333
337
8
Amirthalingam
G
,
Campbell
H
,
Ribeiro
S
, et al
.
Sustained effectiveness of the maternal pertussis immunization program in england 3 years following introduction
.
Clin Infect Dis
.
2016
;
63
(
suppl 4
):
S236
S243
9
Saul
N
,
Wang
K
,
Bag
S
, et al
.
Effectiveness of maternal pertussis vaccination in preventing infection and disease in infants: The NSW Public Health Network case-control study
.
Vaccine
.
2018
;
36
(
14
):
1887
1892
10
Mazagatos
C
,
Godoy
P
,
Muñoz Almagro
C
,
Pozo
F
,
Larrauri
A
;
IVE in Pregnant Women Working Group
.
Effectiveness of influenza vaccination during pregnancy to prevent severe infection in children under 6 months of age, Spain, 2017-2019
.
Vaccine
.
2020
;
38
(
52
):
8405
8410
11
Rowe
SL
,
Perrett
KP
,
Morey
R
, et al
.
Influenza and pertussis vaccination of women during pregnancy in Victoria 2015–2017
.
Med J Aust
.
2019
;
210
(
10
):
454
462
12
Australian Technical Advisory Group on Immunisation (ATAGI)
.
The Australian Immunisation Handbook
. 10th ed.
Canberra, Australia
:
Australian Government Department of Health
;
2017
13
Australian Technical Advisory Group on Immunisation
.
ATAGI clinical advice for immunisation providers regarding maternal vaccination through the NIP
.
14
State Government of Victoria Department of Health and Human Services
.
Pharmacist-administered vaccination services
.
15
Fernández-Cano
MI
,
Espada-Trespalacios
X
,
Reyes-Lacalle
A
, et al
.
Vaccination coverage against pertussis in pregnant women of Catalonia in the first year of implementation of the immunisation program
.
Enferm Infecc Microbiol Clin
.
2017
;
35
(
9
):
550
555
16
Hill
L
,
Burrell
B
,
Walls
T
.
Factors influencing women’s decisions about having the pertussis-containing vaccine during pregnancy
.
J Prim Health Care
.
2018
;
10
(
1
):
62
67
17
Kahn
KE
,
Black
CL
,
Ding
H
, et al
.
Influenza and Tdap vaccination coverage among pregnant women - United States, April 2018
.
MMWR Morb Mortal Wkly Rep
.
2018
;
67
(
38
):
1055
1059
18
Maertens
K
,
Braeckman
T
,
Top
G
,
Van Damme
P
,
Leuridan
E
.
Maternal pertussis and influenza immunization coverage and attitude of health care workers towards these recommendations in Flanders, Belgium
.
Vaccine
.
2016
;
34
(
47
):
5785
5791
19
Public Health England
.
Pertussis Vaccination Programme For Pregnant Women Update: Vaccine Coverage in England, April to June 2018
.
London, United Kingdom
:
Public Health England
;
2018
20
Vizzotti
C
,
Neyro
S
,
Katz
N
, et al
.
Maternal immunization in Argentina: a storyline from the prospective of a middle income country
.
Vaccine
.
2015
;
33
(
47
):
6413
6419
21
Public Health England
.
Pertussis Vaccination Programme for Pregnant Women: Vaccine Coverage in England, January to March 2020 and 2019-20 Annual Coverage
.
London, United Kingdom
:
Public Health England
;
2020
22
Nunes
MC
,
Madhi
SA
.
Influenza vaccination during pregnancy for prevention of influenza confirmed illness in the infants: a systematic review and meta-analysis
.
Hum Vaccin Immunother
.
2018
;
14
(
3
):
758
766
23
Ohfuji
S
,
Deguchi
M
,
Tachibana
D
, et al;
Osaka Pregnant Women Influenza Study Group
.
Protective effect of maternal influenza vaccination on influenza in their infants: a prospective cohort study
.
J Infect Dis
.
2018
;
217
(
6
):
878
886
24
Vygen-Bonnet
S
,
Hellenbrand
W
,
Garbe
E
, et al
.
Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review
.
BMC Infect Dis
.
2020
;
20
(
1
):
136
25
State of Victoria
.
Victoria's Mothers, Babies and Children report 2017
.
26
Public Health and Wellbeing Act, Act No. 46/2008 (Australia)
.
27
Birth Deaths and Marriages Registration Act, Act No. 43/1996 (Australia)
.
28
Australian Immunisation Register Act 2015, Act No. 138/2015. (Australia)
.
Available at: https://www.legislation.gov.au/Details/C2016C00915. Accessed May 31, 2018
29
Queen
MK
.
How to find your perfect match using SAS data management
.
30
Communiable Disease Network Australia
.
Australian national notifiable diseases and case definitions
.
31
Koopman
B
,
Karimi
S
,
Nguyen
A
, et al
.
Automatic classification of diseases from free-text death certificates for real-time surveillance
.
BMC Med Inform Decis Mak
.
2015
;
15
:
53
32
McNutt
L-A
,
Wu
C
,
Xue
X
,
Hafner
JP
.
Estimating the relative risk in cohort studies and clinical trials of common outcomes
.
Am J Epidemiol
.
2003
;
157
(
10
):
940
943
33
Chambers
C
,
Skowronski
DM
,
Sabaiduc
S
, et al
.
Interim estimates of 2015/16 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, February 2016
.
Euro Surveill
.
2016
;
21
(
11
):
30168
34
Sullivan
SG
,
Chilver
MB
,
Carville
KS
, et al
.
Low interim influenza vaccine effectiveness, Australia, 1 May to 24 September 2017
.
Euro Surveill
.
2017
;
22
(
43
):
17
00707
35
Amirthalingam
G
,
Andrews
N
,
Campbell
H
, et al
.
Effectiveness of maternal pertussis vaccination in England: an observational study
.
Lancet
.
2014
;
384
(
9953
):
1521
1528
36
Barug
D
,
Pronk
I
,
van Houten
MA
, et al
.
Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial
.
Lancet Infect Dis
.
2019
;
19
(
4
):
392
401
37
Song
A
,
Sherin
M
,
Cleary
S
,
Spino
C
,
Bernstein
HH
.
maternal self-report of tetanus diphtheria pertussis vaccination during pregnancy correlates with patient-specific electronic medical records [published online ahead of print March 18, 2021]
.
J Pediatr
.
doi:https://doi.org/10.1016/j.jpeds.2021.03.015
38
Mak
DB
,
Regan
AK
,
Vo
DT
,
Effler
PV
.
Antenatal influenza and pertussis vaccination in Western Australia: a cross-sectional survey of vaccine uptake and influencing factors
.
BMC Pregnancy Childbirth
.
2018
;
18
(
1
):
416
39
Baxter
R
,
Bartlett
J
,
Fireman
B
,
Lewis
E
,
Klein
NP
.
Effectiveness of vaccination during pregnancy to prevent infant pertussis
.
Pediatrics
.
2017
;
139
(
5
):
e20164091

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

Supplementary data