Table 1 Characteristics of included studies

Authors and country

Setting/data sources

Study design/ period

Inclusion (I) and exclusion (E) criteria

Intervention/comparison

Final N/ N potentially eligible/ (%)

N Inter-vention group

N Control group

Outcomes

Munoz et al., 2014; USA [30]

3 National Institutes of Health’s Vaccine Treatment Evaluation Units

RCT, 2008–2012

I: Women, 18–45 years of age, with no chronic conditions, a singleton, uncomplicated pregnancy with normal first- or second-trimester screening test results;

E: Women who received Tdap or any tetanus-containing vaccine within the prior 2 years

Tdap (Adacel®) at 30–32 WG vs. placebo

–

33

15

vaccine-related adverse outcomes; perinatal complications; pertussis illness in infants

Hoang et al., 2016; Vietnam [31]

Primary care

RCT, 2012–2013

I: Women, 18–41 years of age, with low risk for complications. E: Women with any serious underlying medical condition; febrile illness within 72 h before injection, receipt of TT vaccine in the past month; receipt of Tdap in the past 10 years; receipt of a vaccine, blood product or experimental medicine 4 weeks before or after injection; previous severe reaction to any vaccine

Tdap (Adacel®) at 20–30 WG vs. TT

–

51

48

short-term vaccine-related adverse outcomes; obstetric and perinatal complications

Halperin et al., 2018; Canada [32]

not specified, most likely outpatient hospital care

RCT, 2007–2014

I: Healthy, pregnant women 18–45 years of age assessed at ≥30 weeks’ gestation to be at low risk for complications; E: Women with high obstetrical risk, history of significant medical disorder or physician-diagnosed pertussis or receipt of Td or Tdap in the last 5 years; sensitivity to Td or Tdap, receipt of blood products or immunoglobulin within 3 months of study entry (except rhesus Ig), or receipt of any vaccines within 2 weeks of study vaccine (except for influenza vaccine).

Tdap (Adacel®) ≥30 WG vs. TT

273/304 (90%)

134

138

acute safety and pregnancy-related outcomes

Berenson et al., 2016; USA [33]

University hospital

RCS, 2012–2014

I: Singleton pregnancies delivered ≥27 WG; E: Women with < 4 clinic visits during pregnancy

Tdap (vaccine not specified) during pregnancy vs. no Tdap

–

1109

650

obstetric and perinatal complications

DeSilva et al., 2016; USA [34]

7 Vaccine Safety Datalink sites (Analysis of health insurance-based electronic health records)

RCS, 2007–2013

I: Singleton live births, women continuously insured from 6 months before LMP through 6 weeks postpartum, with ≥1 outpatient visit(s) during pregnancy. I Infants: birth weight and gestational age available; enrolled in health insurance for ≥4 months in first YoL, with ≥1 outpatient visit(s); E: Infants with exposures increasing risk for structural birth defects (maternal diabetes or use of teratogenic medications, congenital infections, and chromosomal abnormalities)

Tdap (vaccine not specified) during pregnancy vs. no Tdap

324,463 singleton live births

41,654

282,809

microcephaly and other selected major structural birth defects

DeSilva et al., 2017; USA [35]

7 Vaccine Safety Datalink sites (Analysis of health insurance-based electronic health records)

RCS, 2010–2013

I: Singleton live births, women continuously insured from 6 months before LMP through 6 weeks postpartum, with ≥1 outpatient visit(s) during pregnancy. I Infants: birth weight and gestational age available; enrolled in health insurance for ≥4 months in first YoL, with ≥1 outpatient visit(s); E: Women who received live virus vaccines during pregnancy

Tdap mostly at 27–36 WG (vaccine not specified) vs. no Tdap

197,654 /243,981 (81%) live births

45,008

152,556

obstetric and perinatal complications

Donegan et al., 2014; UK [36]

Primary care practices, (650 primary care general practice databases, 12.5 million patients)

RCS, 2012–2013 Tdap- and 2010–2012 control group

I a.) Short-term AE risk: women ≥12 years of age who received pertussis-containing vaccination during pregnancy with ≥28 days of follow-up data after vaccination;

I b.) Risk throughout pregnancy: women ≥12 years of age with a recorded pregnancy outcome and estimated gestational age with follow-up of at least 44 weeks after the date of the LMP.

I Historical cohort: women ≥12 years of age with a recorded pregnancy outcome from October 2010 to September 2012 and no record of a vaccine containing pertussis during or after pregnancy

TdaP-IPV (Repevax®) during pregnancy vs. no ap-vaccine

a.): 17,560/ 20,074 (87%); b.): 6185/20,074 (31%)

18,523

obstetric and perinatal complications

Griffin et al., 2018; New Zealand [37]

Nationwide linked administrative health databases

RCS, 2013

I: All pregnant women who reached 28–38 WG in 2013; E Women: pregnancies < 20 WG or missing maternal or gestational age; E Infants: live born babies < 28 WG or BW < 400 g

Tdap (Boostrix®) at 28–38 WG vs. no Tdap

68,550/73,817 (93%)

8178

60,372

obstetric, perinatal and neonatal outcomes

Kharbanda et al., 2014; USA [38]

2 Vaccine Safety Datalink sites (Analysis of health insurance-based electronic health records)

RCS, 2010–2012

I: Women 14–49  years of age at delivery with singleton pregnancies ending in live birth, continuously insured from 6 months before LMP through 6 weeks postpartum, ≥1 outpatient visit at an affiliated site and with birth weight and gestational age recorded; E: Women who received live virus vaccines during pregnancy or who received Tdap in the 7 days after the estimated pregnancy start date or in the 7 days before delivery; incomplete birth data

Tdap (mainly Adacel®) from 8 days after LMP to 8 days before delivery vs. no Tdap

123,494/300,607 (41%)

26,229

97,265

obstetric and perinatal complications

Kharbanda et al., 2016; USA [39]

Vaccine Safety Datalink sites (Analysis of health insurance-based electronic health records)

RCS, 2007–2013

see Kharbanda, 2014

Tdap (vaccine not specified) during pregnancy vs. no Tdap

427,097/631,256 (68%)

53,885

109,253

acute safety endpoints in 0–42 days after vaccination

Layton et al., 2017; USA [40]

MarketScan Commercial Claims and Encounters (Truven Health Analytics) claims databases of employer-based commercial health care insurance

RCS, 2010–2014

I: Women with livebirth or stillbirth deliveries; only first observed pregnancy per women; E: Women who delivered at ≤26 WG; women ≤18 years in 13 states with universal childhood immunization policies

Tdap (vaccine not specified) at ≥27 WG; Tdap < 27 WG vs. no Tdap

NR

≥27 WG: 123,780 < 27 WG: 25,037

871,177

acute safety endpoints in 0–42 days after vaccination; obstetrical and perinatal complications

Maertens et al., 2016; Belgium [15]

5 hospitals in Antwerp, Belgium

PCS, 2012–2014

I: Women 18–40 years of age with low risk for complications. E: Same as Hoang et al.

Tdap (Boostrix®) at 22–33 WG vs. no Tdap

NR

57

42

acute safety outcomes obstetric and perinatal complications

Morgan et al., 2015; USA [41]

Parkland clinic-based pre-natal and obstetrical care centers in Dallas County with centralized electronic medical charting system

RCS, 2013–2014

I: All women who delivered at Parkland

Tdap (vaccine not specified) at ≥32 WG vs. no Tdap

NR

7152

226

obstetric and neonatal outcomes

Shakib et al., 2013; USA [42]

Intermountain Healthcare database, Utah

RCS, 2005–2009

I: Pregnant women 12–45 years of age and their babies; E: Women whose pregnancy start date could not be determined; women who had documentation of Tdap vaccine within 3 days prior to delivery

Tdap (vaccine not specified) at any time during pregnancy vs. no Tdap

162,448

138

552

obstetric and perinatal complications; congenital anomalies, complex chronic conditions in 1st YoL

Authors/country

Setting/data source

study design/period

Participants (Inclusion (I) and exclusion (E) criteria)

Intervention/comparator

N

Pertussis cases

control group

outcomes

Amirthalingam et al., 2014, UK [43]

notification data from enhanced surveillance for pertussis cases; and sentinel primary care data (Clinical Practice Research Datalink) for vaccination coverage calculations

RCS; screening method, 2008–2013

I: infants < 3 months of age; E: unknown maternal vaccination status, vaccination given within 7 days of birth; first primary infant vaccination before 7 days of disease onset

maternal Tdap-IPV (Repevax®) at 28–38 WG vs. no Tdap

NR

71

26,684

laboratory confirmed pertussis at < 2 and < 3 months of age

Amirthalingam et al., 2016, UK [16]

see Amirthalingam et al., 2014, UK [43]

RCS screening method, 2012–2015

see Amirthalingam et al., 2014, UK [43]

maternal Tdap-IPV (Repevax®, Boostrix-Polio®) at 28–38 WG vs. no Tdap

NR

192

72,781

laboratory confirmed pertussis at < 2 and < 3 months of age; pertussis related deaths

Baxter et al., 2017, USA [44]

Kaiser Permanente Northern California (KPNC) medical care data

RCS, 2010–2015

I: infants born in KPNC hospitals 2010–2015; full term (> = 37 WG); enrolled in Kaiser health plan by age 4 months; mother continuously enrolled in KPNC health plan; mother born before 1996

maternal Tdap vaccination (Boostrix®, Covaxis®) at least 8 days before birth vs. no Tdap

148,981

17

148,964

laboratory confirmed pertussis at < 2 months of age

Becker-Dreps et al., 2018, USA [45]

commercial insurance claims data

RCS, 2010–2014

I: infants </= 18  months of age, delivered between June 2010 and Dec. 2014; First delivery per women; singleton deliveries occurring > 26 WG; E: non-continuous insurance enrolment from pregnancy onset until 7 days post-delivery

maternal Tdap vaccination (vaccine not specified) vs. no Tdap

632,825

112

632,713

laboratory confirmed pertussis at < 2 months of age; pertussis-related hospitalization

Bellido-Blasco et al., 2017, Spain [46]

community-based data; cases were identified via computerized mandatory notification system

CCS, 2015–2016

I: cases: unvaccinated infants < 3 months old, with confirmed pertussis; controls: three paired controls by age (difference less than 15 days) per case; two controls: same paediatrician/family doctor as case; third control: same maternity clinic as case; controls: unvaccinated

maternal Tdap vaccination (vaccine not specified) vs. no Tdap

88

22

66

laboratory confirmed pertussis at < 3 months of age

Dabrera et al., 2015, England and Wales [47]

community-based data; cases were identified via notification system; controls were 2 infants born consecutively after pertussis case from the same practice

CCS, 2012–2013

E infants: aged ≥8 weeks, unknown vaccination status of mother; E controls: known clinical or microbiological diagnosis of pertussis

maternal Tdap-IPV (Repevax®) at any time in pregnancy vs. no Tdap

113

58

55

laboratory confirmed pertussis at <2 months ofage

Saul et al., 2017, Australia [48]

cases were identified via notification system; controls: infant born +/−3 days as case in the maternity clinic of the local health district in which the case was notified

CCS, 2015–2016

E controls: cough illness within two weeks of the onset of the illness in the matched case

maternal Tdap at ≤2 weeks before birth with a 3-component acellular pertussis vaccine vs. no Tdap

96

48

48

laboratory confirmed pertussis at < 3 months of age; pertussis-related hospitalization

Skoff et al., 2017, USA [49]

cases were identified via surveillance in 6 Emerging Infection Program Network sites; controls were hospital-matched

CCS, 2011–2014

I: infants ≥2 days old, residing in the catchment area on their cough onset date, were born in a hospital in their state of residence, were delivered at ≥37 WG, were not adopted or in foster care, and did not live in a residential care facility. E controls: pertussis diagnosis prior to the cough onset date of the corresponding case infant

any pertussis-containing vaccine at any time in pregnancy vs. no Tdap

6252

240

535

laboratory confirmed pertussis at <2 months of age; pertussis-related hospitalization