Politixia
Summary
Background
Pertussis vaccination in pregnancy is recommended in many countries to provide protection to young infants. The best timing for this vaccination is uncertain. In the UK, vaccination is recommended between 16 weeks and 32 weeks of gestation. In this trial we aimed to investigate the equivalence of three time periods for pertussis vaccination in pregnancy.
Methods
Findings
Between May 7, 2019, and Feb 13, 2020, of 1010 women assessed for eligibility, 364 women were recruited and 351 received the intervention (120 in group 1, 119 in group 2, and 112 in group 3). Equivalence of time periods was demonstrated for anti-pertussis toxin and anti-pertactin IgG concentrations. The cord blood geometric mean concentrations of anti-filamentous haemagglutinin IgG were higher with increasing gestational age at vaccination, such that for infants in group 1 (≤23 weeks + 6 days), equivalence to group 3 (28–31 weeks + 6 days) was not shown. Reported rates of fever were similar between study groups.
Interpretation
Pertussis vaccination at three different time intervals in pregnancy resulted in equivalent concentrations of IgG antibodies in infants against two of the three pertussis antigens assessed. Overall, these findings support recommendations to vaccinate any time between 16 weeks and 32 weeks of gestation.
Funding
The Thrasher Research Fund and the National Immunisation Schedule Evaluation Consortium through the National Institute for Health and Care Research policy research programme.
Introduction
In many countries, including those with good vaccine coverage, there was an increase in cases from around 2005, associated with an increase in cases of hospitalisation and death in young infants.
,
In response, pertussis vaccination in pregnancy has been introduced in many countries. Pertussis vaccination in pregnancy increases anti-pertussis IgG in women, which leads to increased transplacental transfer of IgG. This increase results in a higher anti-pertussis IgG concentration in infants, providing protection until they are vaccinated. Pertussis vaccination in pregnancy is safe for both mother and infant,
and effective in preventing pertussis disease, hospitalisation, and death in infants.
,
,
,
However, the best time to offer vaccination in pregnancy to provide optimal protection for infants is debated.
Evidence before this study
We did a systematic review of studies investigating the timing of pertussis vaccination in pregnancy that were published between Jan 1, 2000, and Dec 31, 2019. We searched Embase and MEDLINE on Aug 11, 2022, using the search string “whooping cough” OR “pertussis” AND “maternal vaccination” OR “antenatal vaccination” OR “vaccination in pregnancy” OR “vaccination during pregnancy” AND “timing” OR “time interval” OR “gestational age” OR “gestation” and MESH terms “Bordetella pertussis” and “maternal vaccination”, restricted to English-language papers only. We found no randomised controlled trials and six observational studies. In terms of antibody concentrations, two trials showed superiority of early third-trimester vaccination compared with vaccination later in the third trimester, whereas one trial showed no difference between these time periods and one further study showed that second trimester vaccination was superior to vaccination in the third trimester. Two studies investigated antibody avidity; one showed increased avidity of antibodies with increasing gestation at vaccination, whereas the other reported reduced avidity of antibodies with increasing gestation.
Added value of this study
We report the results of the first randomised controlled trial to investigate the effect of timing of pertussis vaccination in pregnancy on infant antibody concentrations. We found that for the three time intervals considered, antibody concentrations to two of the three pertussis antigens were equivalent (pertussis toxin and pertactin), whereas for one antigen (filamentous haemagglutinin), vaccination at 28–32 weeks of gestation resulted in higher antibody concentrations than vaccination earlier than 24 weeks of gestation.
Implications of all the available evidence
A wider time interval for pertussis vaccination in pregnancy might allow for higher vaccine coverage and improved protection for infants born prematurely. Considered together with vaccine effectiveness data, the evidence from this trial supports vaccination of pregnant women at any time between 16 weeks and 32 weeks of gestation.
In the UK, the initial recommendation was to administer the vaccine at 28–32 weeks of gestation because of concerns that the rapid rate of decay of pertussis-specific IgG would result in less protection for the infant if vaccination was administered earlier.
An Australian study found that anti-pertussis toxin IgG concentrations were significantly higher in the cord blood of neonates born to mothers vaccinated at 28–32 weeks of gestation than in those born to mothers vaccinated at 33–36 weeks of gestation, with higher IgG avidity.
,
Another prospective cohort study showed that vaccination at 27–31 weeks of gestation resulted in higher anti-pertussis toxin antibody concentrations at birth than vaccination at 32–36 weeks of gestation, with concentrations increasing from 27 weeks to 30 weeks of gestation.
Finally, an observational study from Switzerland in 2016 showed that anti-pertussis toxin and anti-filamentous haemagglutinin concentrations were higher in cord blood following vaccination in the second trimester than following vaccination in the third trimester.
Following this report, and mindful of the logistical benefits of offering vaccination in a wider time window, the UK extended the recommended window for vaccination to 16–32 weeks in 2016.
,
whereas another study showed no effect of timing of vaccination on protection.
We did an open-label, equivalence, randomised controlled trial to investigate the effect of timing of vaccine administration in pregnancy on the immunogenicity of a combined diphtheria, tetanus, and acellular pertussis (TdaP) vaccine.
Methods
Study design and participants
We recruited from six UK sites: St George’s University Hospitals UK National Health Service (NHS) Foundation Trust, Kingston Hospital NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust, Oxford University Hospitals NHS Foundation Trust, University Hospitals Bristol NHS Foundation Trust, and Manchester University NHS Foundation Trust.
Participants were approached by letter, or as they attended routine antenatal care. All participants were recruited before 23 weeks + 6 days of gestation. Women were eligible to participate if they were pregnant and had not received pertussis vaccination in the current pregnancy, if they were willing and able to take part in the study and provide informed consent, and if they had a routine anomaly ultrasound scan at 20 weeks with no evidence of life-limiting congenital abnormalities. Women were excluded from participation if they were younger than 16 years, if they had confirmed or suspected pertussis infection in the previous 5 years (identified through directed questions at the screening visit), if they had a known immune deficiency or had received immunosuppressive medication within 6 months of screening, or if, in the opinion of the investigator, they were unlikely to complete follow-up.
Randomisation and masking
A computerised block-randomisation list was produced by the study statistician and participants were randomly assigned on a 1:1:1 ratio to one of the three following timing groups: group 1 (≤23 weeks + 6 days), group 2 (24–27 weeks + 6 days) and group 3 (28–31 weeks + 6 days). Group allocations were placed inside opaque envelopes bearing the corresponding participant number by staff not involved in the trial. Each centre was provided with the necessary envelopes and on recruitment to the study each participant was allocated, in order of inclusion, the next available participant number. There was no masking in the clinic. Participants and research staff were aware of the group allocation; however, laboratory staff who did the testing were not.
Procedures
At the screening visit randomisation took place and the timing of the vaccination visit was assigned. At the vaccination visit a baseline blood sample was collected before the participants received Boostrix-inactivated poliovirus vaccine (GlaxoSmithKline; London, UK). Boostrix-IPV contains pertussis toxin (8 μg), filamentous haemagglutinin (8 μg), pertactin (2·5 μg), diphtheria toxoid (not less than two international units), tetanus toxoid (not less than 20 international units), and inactivated polio virus types 1–3 (type-1 40 D-antigen unit, type-2 8 D-antigen unit, and type-3 32 D-antigen unit). Following vaccination, participants received a diary card for the 7 days following vaccination. A blood sample was collected 2 weeks following vaccination, together with the completed diary card, and participants were asked about adverse events. Following delivery, a cord sample and maternal sample were collected. If a cord sample was not obtained, parents were asked for permission to collect a sample from the infant within the first week of life. All infants were vaccinated in primary care according to the UK national schedule which included diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, haemophilus influenzae type B vaccine (Infanrix hexa; GlaxoSmithKline) at 2 months, 3 months, and 4 months of age. An infant visit then took place 28–70 days following completion of the primary vaccination series, at which details of vaccination, history of respiratory illness, or contact with cases of pertussis were recorded and a blood sample was collected. Maternal adverse events, which occurred within 28 days of vaccine administration, and medically attended adverse events or serious adverse events occurring during study participation for mother or infant were recorded.
Outcomes
Our primary objective was to determine whether pertussis vaccination at three different time intervals in pregnancy results in equivalent concentrations of pertussis-specific IgG in the term infant at birth. Our secondary objectives were as follows: to determine whether pertussis vaccination at different time intervals in pregnancy resulted in equivalent concentrations of pertussis-specific antibodies in the preterm infant at birth; to investigate the incidence of fever and local reactions in women receiving the vaccine in pregnancy who had not within 5 years or within a previous pregnancy received a pertussis-containing vaccine compared with those who had; to describe the kinetics of the antibody response to pertussis vaccination during pregnancy; to describe the transplacental transfer ratio of antibody following administration of vaccine at different timepoints; to explore the effect of repeated vaccination on the antibody response in women who had within 5 years or within a previous pregnancy received a pertussis vaccination; and to evaluate the effect of timing of pertussis vaccination in pregnancy on antibody concentrations in infants following their primary immunisation schedule.
Outcome assessment
These concentrations were measured relative to the first WHO International Pertussis Standard Serum (06/140, National Institute for Biological Standards and Control). There is no correlation between specific concentrations of antibody against pertussis antigens and protection against pertussis disease. However, Eberhardt and colleagues
described a method of defining infant seropositivity in which infants who were born with an anti-pertussis toxin concentration of more than 30 IU/mL were calculated to have antibody concentrations higher than 5 IU/mL until at least 3 months of age. As an additional exploratory analysis, we therefore compared the percentage of infants in each group that had anti-pertussis toxin concentrations higher than 30 IU/mL at birth, and these infants were considered to be seropositive.
Participants completed a diary card for 7 days following vaccination, which included recording their temperature and any local reactions once per day.
Statistical analysis
We calculated sample size using previous studies of cord blood, which showed the log10 SD to be about 0·50 for pertussis toxin, 0·40 for filamentous haemagglutinin, and 0·55 for pertactin. To assess equivalence within a 1·8-fold margin, and assuming the higher standard deviation of 0·55, we calculated that 100 women per group would be needed (two-sided 95% CI on the fold difference to assess equivalence, 80% power), which, allowing for a dropout rate of around 10% and a rate of prematurity of around 8%, would require recruitment of 354 women. Missing data were assumed to be missing at random and there was no imputation. The analysis was done per protocol. For reactogenicity, the analysis set included all women who received a dose of vaccine.
Role of the funding source
The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Results
Figure 1CONSORT flow diagram for participants
Table 1Baseline characteristics of participants
Figure 2GMC (IU/mL) and 95% CI of IgG against filamentous haemagglutinin, pertactin, and pertussis toxin in cord blood of infants born at term according to study group
GMC=geometric mean concentration. FHA=filamentous haemagglutinin. PT=pertussis toxin. PRN=pertactin.
There was no significant difference in infants born at term reaching seropositivity between study groups (group 1, 74 [75·5%] of 98; group 2, 75 [80·7%] of 93; and group 3, 71 [83·5%] of 85; p=0·40).
Table 2GMCs for filamentous haemagglutinin, pertactin, and pertussis toxin immunoglobulin G in maternal samples before and 2 weeks after vaccination and at delivery
GMC=geometric mean concentration.
Figure 3GMC (IU/mL) and 95% CI for filamentous haemagglutinin, pertactin, and pertussis toxin immunoglobulin G according to recent vaccination status before and after receiving study vaccine
FHA=filamentous haemagglutinin. GMC=geometric mean concentration. PT=pertussis toxin. PRN=pertactin.
Table 3Reported local reactions or fever according to group
Data are presented as percentage (95% CI). Redness and swelling were mild if 2·5–5 cm, moderate if 5·1–10 cm, and severe if more than 10 cm. Fever was mild if 38–38·4°C, moderate if 38·5–38·9°C, and severe if higher than 39°C.
Discussion
We report, to our knowledge for the first time, the results of a randomised controlled trial investigating the timing of pertussis vaccination during pregnancy on cord blood pertussis antigen-specific IgG GMCs. We found that the equivalence criteria were met for anti-pertussis toxin and anti-pertactin antibody concentrations between babies born to mothers vaccinated at different time intervals, but there were higher anti-filamentous haemagglutinin antibody concentrations in babies born to mothers vaccinated at 28–32 weeks of gestation, compared with those vaccinated at less than 24 weeks of gestation.
Of note, this study included the whole of the third trimester (≥26 weeks) rather than the early third-trimester period used in our study (28–32 weeks). There have been several reports suggesting that vaccination in the early third trimester is superior to that of vaccination later in the third trimester,
,
,
,
which might explain this difference.
Furthermore, a UK observational study
has shown similar effectiveness against pertussis in infants following vaccination at different times in the second and third trimesters. These clinical data support our findings and suggest that the observed differences in anti-filamentous haemagglutinin antibody concentrations might not be of clinical significance.
Preterm infants are at an increased risk of severe pertussis,
,
but they are less likely to benefit from vaccination when this is administered later in pregnancy.
A UK observational study has shown that broadening the gestational age window at which antenatal pertussis vaccination is offered in the routine programme has been associated with a reduction in pertussis hospitalisations in preterm infants, although the number of preterm infants admitted both before and after the broadening of the window for vaccination was small.
We are unable to draw any conclusions about the effect of timing of maternal vaccination in infants born preterm because of the small numbers of such infants in our study. Another advantage of having a broad time window in which to offer vaccination is that it increases the opportunities for a vaccine to be administered.
The reason for higher anti-filamentous haemagglutinin IgG concentrations at birth in neonates born to mothers vaccinated at 28–32 weeks of gestation appears to be a better initial response in women vaccinated in the third trimester (of statistical significance for group 3 [28–31 weeks + 6 days] vs group 1 [≤23 weeks + 6 days]) combined with a shorter interval to delivery resulting in less time for antibody waning. The combination of these factors means that antibody concentrations are subsequently higher through the third trimester and at delivery in both the mother and the baby. The differences in anti-filamentous haemagglutinin antibody concentrations at birth do not appear to reflect any differences in placental transfer ratios according to the timing of vaccination.
in using an infant seropositivity calculation to assess the proportions of infants in each group who could be assumed to have protection until around 3 months, at which time they should be starting to benefit from their own vaccinations. We found no differences between the three study groups in this assessment of protection, suggesting that vaccination at any time between 19 weeks and 32 weeks might provide equivalent protection for young infants.
,
The clinical significance of this finding is uncertain. In keeping with a meta-analysis,
we found that the timing of vaccination in pregnancy did not lead to a significant difference in antibody concentrations following primary vaccinations. However, there was notable attrition at the later study timepoints, so these findings should be further investigated with a larger sample size.
,
We identified an increase in reported local tenderness in women who had been vaccinated recently, but no increase in other local reactions or in the incidence of fever. We found that women who had recently been vaccinated, either in pregnancy or for other reasons, had higher antibody GMCs before vaccination. This finding is in keeping with previous work.
Because there is no correlate of protection, it is not possible to conclude whether participants who had previously been vaccinated might have had sufficient protection for themselves, or their babies, in the absence of another vaccination dose in pregnancy. However, data from the UK showed a lower effectiveness of 44% (95% CI 19–75) in those vaccinated only in a previous pregnancy, and therefore it can be concluded that vaccination in every pregnancy should still be advised.
Although there was equivalence in higher anti-pertussis toxin and anti-pertactin antibody concentrations in the infant at birth, we did not investigate the avidity of these antibodies. It is possible that earlier vaccination results in higher avidity (or affects antibody function in another way), and this avidity is something which should be investigated further. As one of our exploratory objectives we are investigating the functional performance of the antibody using serum bactericidal antibody assays.
The follow-up phase of the study was substantially affected by the COVID-19 pandemic. The pandemic had a particular impact on the collection of infant samples, limiting the power of this aspect of the study (albeit a secondary objective). We used gestational age windows that were within the timeframe currently recommended in the UK, which means we are unable to comment on vaccination earlier in the second trimester or later in the third trimester. Information about which pertussis-containing vaccines participants had previously received was not collected, which means we are unable to comment on differences in response in women who had been primed with whole-cell versus acellular vaccine, or with a different acellular vaccine to the one they received in this trial. The vast majority of the participants will have received whole-cell pertussis vaccines in infancy.
We used broad eligibility criteria and recruited women attending hospital for routine antenatal care to recruit as representative a population as possible. However, the percentage of participants in this trial who were of non-White ethnicity was lower than in the pregnant UK population.
In the first randomised controlled trial to investigate the timing of pertussis vaccination in pregnancy on antibody concentrations in infants, we have shown that for two of the three antigens tested, there was equivalence of vaccination across the three time periods.
Considered together with recent vaccine effectiveness data, these results support the current guidance to vaccinate pregnant women any time between 16 weeks and 32 weeks of gestation.
OpTIMUM study group
Agnieszka Burtt, Wendy Byrne, Angelika Capp, Lotoyah Carty, Krina Chawla, Sarah Collins, Emily Cornish, Olwenn Daniel, Jessica Fretwell, Andrew Gorringe, Teresa Gubbins, Tom Hall, Susan Johnston, Uzma Khan, Suzy Lim, Nicki Martin, Ella Morey, Jude Mossop, Katie O’Brien, Nelly Owino, Deborah Powell, Laxmee Ramkhelawon, Helen Ratcliffe, Hannah Roberts, Fenella Roseman, Laura Sparks, Lorraine Stapley, Stephen Taylor, Fiona Walbridge, Rosie Watts, Susan J Wellstead, and Tabitha Wishlade.
Contributors
AC, PTH, KLD, and CEJ conceived of the study. PTH was the lead applicant for funding and NA, AC, CEJ, AK, and KLD were coapplicants. AC, PTH, KLD, CEJ, GA, NA, SB, MC, BH, EJ, AK, MM, EP, MDS, and MV contributed to the study design. AC, SB, MC, HC, AE, VG, EJ, CEJ, KK, MM, EP, MDS, MV, and PTH were involved in the project administration. AC, KK, and VG did the data curation. MM, HC, and AE were responsible for sample testing. NA developed the statistical analysis plan and did the statistical analysis. AC, PTH, and NA accessed and verified the underlying data and drafted the manuscript. All authors reviewed and edited the manuscript and gave final approval for the version to be published.
Data sharing
Declaration of interests
GA and NA report that the Immunisation and Vaccine Preventable Diseases Division has provided vaccine manufacturers with postmarketing surveillance reports on pneumococcal and meningococcal infection, which the companies are required to submit to the UK Licensing Authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. CEJ has done studies on behalf of the University of Southampton and University Hospital Southampton NHS Foundation Trust funded by vaccine manufacturers, including Novavax, Moderna, Medicago, and Pfizer, but receives no personal funding for these activities. CEJ has served on advisory boards, data safety monitoring boards, or as a consultant for Moderna, MSD, Sanofi, Minervax, and Pfizer. MDS has acted as an investigator on behalf of the University of Oxford for studies funded or supported by vaccine manufacturers including GlaxoSmithKline, Pfizer, MCM vaccines, Novavax, AstraZeneca, and Janssen. MDS received no direct financial benefit for this work. From September, 2022 (after completion of this work), MDS became an employee of Medimmune and Moderna. PTH has conducted studies on behalf of St George’s, University of London funded by vaccine manufacturers, including AstraZeneca, Novavax, Moderna, Valneva, Janssen, Minervax, and Pfizer, but receives no personal funding for these activities. All other authors declare no competing interests.
Acknowledgments
We gratefully acknowledge all of the participants of the study and the clinical teams at the participating sites. This study is an independent research study funded by the Thrasher Research Fund (award number 14390) and the National Immunisation Schedule Evaluation Consortium (NISEC) through the National Institute for Health and Care Research policy research programme (award ID PR-R17-0916-22001). The views expressed are those of the authors and not necessarily those of the NISEC or the National Institute for Health and Care Research policy research programme.
Supplementary Material
References
- 1.
Pertussis immunisation and control in England and Wales, 1957 to 2012: a historical review.
Euro Surveill. 2012; 18: 38
- 2.
Investigating the pertussis resurgence in England and Wales, and options for future control.
BMC Med. 2016; 14: 121
- 3.
Pertussis resurgence: perspectives from the Working Group Meeting on pertussis on the causes, possible paths forward, and gaps in our knowledge.
J Infect Dis. 2014; 209: S32-S35
- 4.
Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review.
BMC Infect Dis. 2020; 20: 136
- 5.
Effectiveness of maternal pertussis vaccination in England: an observational study.
Lancet. 2014; 384: 1521-1528
- 6.
Sustained effectiveness of the maternal pertussis immunization program in England 3 years following introduction.
Clin Infect Dis. 2016; 63: S236-S243
- 7.
Effectiveness of prenatal tetanus, diphtheria, acellular pertussis vaccination in the prevention of infant pertussis in the US.
Am J Prev Med. 2018; 55: 159-166
- 8.
The effect of timing of maternal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.
Vaccine. 2014; 32: 5787-5793
- 9.
The effect of timing of tetanus-diphtheria-acellular pertussis vaccine administration in pregnancy on the avidity of pertussis antibodies.
Front Immunol. 2019; 102423
- 10.
The optimal gestation for pertussis vaccination during pregnancy: a prospective cohort study.
Am J Obstet Gynecol. 2016; 215: 237e1-237e6
- 11.
Association between third-trimester Tdap immunization and neonatal pertussis antibody concentration.
JAMA. 2018; 320: 1464-1470
- 12.
Maternal immunization earlier in pregnancy maximizes antibody transfer and expected infant seropositivity against pertussis.
Clin Infect Dis. 2016; 62: 829-836
- 13.
Effectiveness of prenatal versus postpartum tetanus, diphtheria, and acellular pertussis vaccination in preventing infant pertussis.
Clin Infect Dis. 2017; 64: 3-8
- 14.
Impact of the US maternal tetanus, diphtheria, and acellular pertussis vaccination program on preventing pertussis in infants <2 months of age: a case-control evaluation.
Clin Infect Dis. 2017; 65: 1977-1983
- 15.
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: 380-387
- 16.
Optimising the Timing of whooping cough Immunisation in MUMs: a randomised controlled trial investigating the timing of pertussis vaccination in pregnancy (OpTIMUM): a protocol paper.
Wellcome Open Res. 2021; 6: 152
- 17.
Serum IgG, IgA, and IgM responses to pertussis toxin, filamentous hemagglutinin, and agglutinogens 2 and 3 after infection with Bordetella pertussis and immunization with whole-cell pertussis vaccine.
J Infect Dis. 1989; 160: 838-845
- 18.
Acellular pertussis vaccines induce anti-pertactin bactericidal antibodies which drives the emergence of pertactin-negative strains.
Front Microbiol. 2020; 112108
- 19.
Optimisation of timing of maternal pertussis immunisation from 6 years of post-implementation surveillance data in England.
Clin Infect Dis. 2022; 6: e1129-e1139
- 20.
Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness.
BMC Infect Dis. 2019; 19: 919
- 21.
Hospitalisation of preterm infants with pertussis in the context of a maternal vaccination programme in England.
Arch Dis Childhood. 2018; 103: 224-229
- 22.
Current antenatal pertussis vaccination guidelines miss preterm infants: an epidemiological study from the Northern Territory.
Aus New Zealand J Obstetr Gynaecol. 2019; 59: 436-443
- 23.
Impact of extending the timing of maternal pertussis vaccination on hospitalized infant pertussis in England, 2014–2018.
Clin Infect Dis. 2021; 73: e2502-e2508
- 24.
Optimal timing of influenza vaccine during pregnancy: a systematic review and meta-analysis.
Influenza Other Respir Viruses. 2019; 13: 438-452
- 25.
Factors affecting antibody responses to immunizations in infants born to women immunized against pertussis in pregnancy and unimmunized women: individual-participant data meta-analysis.
Vaccine. 2021; 39: 6545-6552
- 26.
A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants.
BMC Med. 2021; 19: 138
- 27.
Pertussis vaccination in pregnancy.
Hum Vaccin Immunother. 2016; 12: 1972-1981
- 28.
Association of Tdap vaccination with acute events and adverse birth outcomes among pregnant women with prior tetanus-containing immunizations.
JAMA. 2015; 314: 1581-1587
- 29.
The decline of pertussis-specific antibodies after tetanus, diphtheria, and acellular pertussis immunization in late pregnancy.
J Infect Dis. 2015; 212: 1869-1873
Article info
Publication history
Published: April 17, 2023
Identification
Copyright
© 2022 The Author(s). Published by Elsevier Ltd.
