Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement

Bahaa Abu-Raya, Kirsten Maertens, Kathryn M Edwards, Saad B Omer, Janet A Englund, Katie L Flanagan, Matthew D Snape, Gayatri Amirthalingam, Elke Leuridan, Pierre Van Damme, Vana Papaevangelou, Odile Launay, Ron Dagan, Magda Campins, Anna Franca Cavaliere, Tiziana Frusca, Sofia Guidi, Miguel O'Ryan, Ulrich Heininger, Tina Tan, Ahmed R Alsuwaidi, Marco A Safadi, Luz M Vilca, Nasamon Wanlapakorn, Shabir A Madhi, Michelle L Giles, Roman Prymula, Shamez Ladhani, Federico Martinón-Torres, Litjen Tan, Lessandra Michelin, Giovanni Scambia, Nicola Principi, Susanna Esposito, Bahaa Abu-Raya, Kirsten Maertens, Kathryn M Edwards, Saad B Omer, Janet A Englund, Katie L Flanagan, Matthew D Snape, Gayatri Amirthalingam, Elke Leuridan, Pierre Van Damme, Vana Papaevangelou, Odile Launay, Ron Dagan, Magda Campins, Anna Franca Cavaliere, Tiziana Frusca, Sofia Guidi, Miguel O'Ryan, Ulrich Heininger, Tina Tan, Ahmed R Alsuwaidi, Marco A Safadi, Luz M Vilca, Nasamon Wanlapakorn, Shabir A Madhi, Michelle L Giles, Roman Prymula, Shamez Ladhani, Federico Martinón-Torres, Litjen Tan, Lessandra Michelin, Giovanni Scambia, Nicola Principi, Susanna Esposito

Abstract

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B Streptococcus vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant.

Keywords: group B Streptococcus vaccines; influenza; maternal immunization; pertussis; pregnant women; respiratory syncytial virus; tetanus.

Copyright © 2020 Abu-Raya, Maertens, Edwards, Omer, Englund, Flanagan, Snape, Amirthalingam, Leuridan, Damme, Papaevangelou, Launay, Dagan, Campins, Cavaliere, Frusca, Guidi, O'Ryan, Heininger, Tan, Alsuwaidi, Safadi, Vilca, Wanlapakorn, Madhi, Giles, Prymula, Ladhani, Martinón-Torres, Tan, Michelin, Scambia, Principi and Esposito.

Figures

Figure 1
Figure 1
Countries with recommendations for immunization against pertussis in pregnancy by official authorities (for South America, pertussis immunization during pregnancy is recommended by The Pan American Health Organization). This figure was inspired by G. Amirthalingham and K. Maertens and created by K. Maertens.
Figure 2
Figure 2
A summary of the major factors affecting vaccination in pregnancy. Created by Claudio Rosa.

References

    1. Esposito S, Bosis S, Morlacchi L, Baggi E, Sabatini C, Principi N. Can infants be protected by means of maternal vaccination? Clin Microbiol Infect. (2012) 18:85–92. 10.1111/j.1469-0691.2012.03936.x
    1. Marchant A, Sadarangani M, Garand M, Dauby N, Verhasselt V, Pereira L, et al. . Maternal immunisation: collaborating with mother nature. Lancet Infect Dis. (2017) 17:e197–208. 10.1016/S1473-3099(17)30229-3
    1. Thwaites CL, Beeching NJ, Newton CR. Maternal and neonatal tetanus. Lancet. (2015) 385:362–70. 10.1016/S0140-6736(14)60236-1
    1. Campbell H, Gupta S, Dolan GP, Kapadia SJ, Kumar Singh A, Andrews N, Amirthalingam G. Review of vaccination in pregnancy to prevent pertussis in early infancy. J Med Microbiol. (2018) 67:1426–56. 10.1099/jmm.0.000829
    1. Esposito S, Stefanelli P, Fry NK, Fedele G, He Q, Paterson P, et al. . Pertussis prevention: reasons for resurgence, and differences in the current acellular pertussis vaccines. Front Immunol. (2019) 10:1344. 10.3389/fimmu.2019.01344
    1. Amirthalingam G, Andrews N, Campbell H, Ribeiro S, Kara E, Donegan K, et al. . Effectiveness of maternal pertussis vaccination in England: an observational study. Lancet. (2014) 384:1521–8. 10.1016/S0140-6736(14)60686-3
    1. Baxter R, Bartlett J, Fireman B, Lewis E, Klein NP. Effectiveness of vaccination during pregnancy to prevent infant pertussis. Pediatrics. (2017) 139:e20164091. 10.1542/peds.2016-4091
    1. Abu Raya B, Edwards KM, Scheifele DW, Halperin SA. Pertussis and influenza immunisation during pregnancy: a landscape review. Lancet Infect Dis. (2017) 17:e209–22. 10.1016/S1473-3099(17)30190-1
    1. Leuridan E, Nunes M, Jones C. Maternal Immunization. 1st ed. Academic Press.
    1. Heath PT, Culley FJ, Jones CE, Kampmann B, Le Doare K, Nunes MC, et al. Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis. Lancet Infect Dis. (2017) 17:e223–34. 10.1016/S1473-3099(17)30232-3
    1. Esposito S, Pietro GD. Respiratory syncytial virus vaccines: an update on those in the immediate pipeline. Fut Microbiol. (2016) 11:1479–90. 10.2217/fmb-2016-0106
    1. A Roadmap for Advancing RSV Maternal Immunization. (2018) Available online at: . accessed December 4th, 2019.
    1. Overcoming barriers and identifying opportunities for developing maternal immunizations: recommendations from the National Vaccine Advisory Committee Public Health Rep. (2017) 132:271–84. 10.1177/0033354917698118
    1. Beigi RH, Omer SB, Thompson KM. Key steps forward for maternal immunization: policy making in action. Vaccine. (2018) 36:1521–3. 10.1016/j.vaccine.2018.02.041
    1. Chamberlain AT, Lavery JV, White A, Omer SB. Ethics of maternal vaccination. Science. (2017) 358:452–3. 10.1126/science.aao4219
    1. Pregnant Women and Vaccines Against Emerging Epidemic Threats. Ethics Guidance for Preparedness, Research and Response. The Prevent Working Group. Available online at: (accessed January 28, 2020).
    1. Vaccines against influenza WHO position paper – November 2012 Wkly Epidemiol Rec. (2012) 87:461–76. Available online at:
    1. Meeting of the Strategic Advisory Group of Experts on immunization, April 2015: conclusions and recommendations Wkly Epidemiol Rec. (2015) 90:261–78. Available online at:
    1. Munoz FM, Eckert LO, Katz MA, Lambach P, Ortiz JR, Bauwens J, et al. . Key terms for the assessment of the safety of vaccines in pregnancy: results of a global consultative process to initiate harmonization of adverse event definitions. Vaccine. (2015) 33:6441–52. 10.1016/j.vaccine.2015.07.112
    1. Bonhoeffer J, Kochhar S, Hirschfeld S, Heath PT, Jones CE, Bauwens J, et al. Global alignment of immunization safety assessment in pregnancy - the GAIA project. Vaccine. (2016) 34:5993–7. 10.1016/j.vaccine.2016.07.006
    1. Rouse CE, Eckert LO, Muñoz FM, Stringer JSA, Kochhar S, Bartlett L, et al. Postpartum endometritis and infection following incomplete or complete abortion: case definition & guidelines for data collection, analysis, presentation of maternal immunization safety data. Vaccine. (2019) 37:7585–95. 10.1016/j.vaccine.2019.09.101
    1. Pellegrin S, Munoz FM, Padula M, Heath PT, Meller L, Top K, et al. . Neonatal seizures: case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. (2019) 37:7596–609. 10.1016/j.vaccine.2019.05.031
    1. Kachikis A, Eckert LO, Walker C, Bardají A, Varricchio F, Lipkind HS, et al. . Chorioamnionitis: case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. (2019) 37:7610–22. 10.1016/j.vaccine.2019.05.030
    1. Villagomez AN, Muñoz FM, Peterson RL, Colbert AM, Gladstone M, MacDonald B, et al. . Neurodevelopmental delay: case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. (2019) 37:7623–41. 10.1016/j.vaccine.2019.05.027
    1. Pazos M, Sperling RS, Moran TM, Kraus TA. The influence of pregnancy on systemic immunity. Immunol Res. (2012) 54:254–61. 10.1007/s12026-012-8303-9
    1. Lima J, Martins C, Leandro MJ, Nunes G, Sousa MJ, Branco JC, et al. . Characterization of B cells in healthy pregnant women from late pregnancy to post-partum: a prospective observational study. BMC Pregn Childbirth. (2016) 16:139. 10.1186/s12884-016-0927-7
    1. Medina KL, Smithson G, Kincade PW. Suppression of B lymphopoiesis during normal pregnancy. J Exp Med. (1993) 178:1507–15. 10.1084/jem.178.5.1507
    1. Medina KL, Kincade PW. Pregnancy-related steroids are potential negative regulators of B lymphopoiesis. Proc Natl Acad Sci USA. (1994) 91:5382–6. 10.1073/pnas.91.12.5382
    1. Birkeland SA, Kristoffersen K. Lymphocyte transformation with mitogens and antigens during normal human pregnancy: a longitudinal study. Scand J Immunol. (1980) 11:321–5. 10.1111/j.1365-3083.1980.tb00240.x
    1. Lima J, Cambridge G, Vilas-Boas A, Martins C, Borrego LM, Leandro M. Serum markers of B-cell activation in pregnancy during late gestation, delivery, and the postpartum period. Am J Reprod Immunol. (2019) 81:e13090. 10.1111/aji.13090
    1. Larsson A, Palm M, Hansson LO, Basu S, Axelsson O. Reference values for alpha1-acid glycoprotein, alpha1-antitrypsin, albumin, haptoglobin, C-reactive protein, IgA, IgG and IgM during pregnancy. Acta Obstet Gynecol Scand. (2008) 87:1084–8. 10.1080/00016340802428146
    1. Kourtis AP, Read JS, Jamieson DJ. Pregnancy and infection. N Engl J Med. (2014) 370:2211–18. 10.1056/NEJMra1213566
    1. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today. (1993) 14:353–6. 10.1016/0167-5699(93)90235-D
    1. Saito S. Cytokine network at the feto-maternal interface. J Reprod Immunol. (2000) 47:87–103. 10.1016/S0165-0378(00)00060-7
    1. Piccinni MP, Giudizi MG, Biagiotti R, Beloni L, Giannarini L, Sampognaro S, et al. . Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J Immunol. (1995) 155:128–33.
    1. Raghupathy R, Makhseed M, Azizieh F, Omu A, Gupta M, Farhat R. Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod. (2000) 15:713–18. 10.1093/humrep/15.3.713
    1. Glassman AB, Bennett CE, Christopher JB, Self S. Immunity during pregnancy: lymphocyte subpopulations and mitogen responsiveness. Ann Clin Lab Sci. (1985) 15:357–62.
    1. Fujisaki S, Mori N, Sasaki T, Maeyama M. Cell-mediated immunity in human pregnancy: changes in lymphocyte reactivity during pregnancy and postpartum. Microbiol Immunol. (1979) 23:899–907. 10.1111/j.1348-0421.1979.tb02823.x
    1. Marzi M, Vigano A, Trabattoni D, Villa ML, Salvaggio A, Clerici E, et al. . Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy. Clin Exp Immunol. (1996) 106:127–33. 10.1046/j.1365-2249.1996.d01-809.x
    1. Brabin BJ, Nagel J, Hagenaars AM, Ruitenberg E, van Tilborgh AM. The influence of malaria and gestation on the immune response to one and two doses of adsorbed tetanus toxoid in pregnancy. Bull World Health Organ. (1984) 62:919–30.
    1. Huygen K, Caboré RN, Maertens K, Van Damme P, Leuridan E. Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women. Vaccine. (2015) 33:4117–23. 10.1016/j.vaccine.2015.06.108
    1. Hulka JF. Effectiveness of polyvalent influenza vaccine in pregnancy. Report of a controlled study during an outbreak of Asian influenza. Obstet Gynecol. (1964) 23:830–7.
    1. Murray DL, Imagawa DT, Okada DM, St. Geme JW. Antibody response to monovalent A/New Jersey/8/76 influenza vaccine in pregnant women. J Clin Microbiol. (1979) 10:184–7. 10.1128/JCM.10.2.184-187.1979
    1. Tsatsaris V, Capitant C, Schmitz T, Chazallon C, Bulifon S, Riethmuller D, et al. . Maternal immune response and neonatal seroprotection from a single dose of a monovalent nonadjuvanted 2009 influenza A(H1N1) vaccine: a single-group trial. Ann Intern Med. (2011) 155:733–41. 10.7326/0003-4819-155-11-201112060-00005
    1. Schlaudecker EP, Ambroggio L, McNeal MM, Finkelman FD, Way SS. Declining responsiveness to influenza vaccination with progression of human pregnancy. Vaccine. (2018) 36:4734–41. 10.1016/j.vaccine.2018.05.117
    1. Bischoff AL, Folsgaard NV, Carson CG, Stokholm J, Pedersen L, Holmberg M, et al. . Altered response to A(H1N1)pnd09 vaccination in pregnant women: a single blinded randomized controlled trial. PLoS ONE. (2013) 8: e56700. 10.1371/journal.pone.0056700
    1. Schlaudecker EP, McNeal MM, Dodd CN, Ranz JB, Steinhoff MC. Pregnancy modifies the antibody response to trivalent influenza immunization. J Infect Dis. (2012) 206:1670–3. 10.1093/infdis/jis592
    1. Kay AW, Fukuyama J, Aziz N, Dekker CL, Mackey S, Swan GE, et al. . Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy. Proc Natl Acad Sci USA. (2014) 111:14506–11. 10.1073/pnas.1416569111
    1. Simister NE. Placental transport of immunoglobulin G. Vaccine. (2003) 21:3365–9. 10.1016/S0264-410X(03)00334-7
    1. Saji F, Samejima Y, Kamiura S, Koyama M. Dynamics of immunoglobulins at the feto-maternal interface. Rev Reprod. (1999) 4:81–9. 10.1530/ror.0.0040081
    1. Malek A, Sager R, Kuhn P, Nicolaides KH, Schneider H. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol. (1996) 36:248–55. 10.1111/j.1600-0897.1996.tb00172.x
    1. Kohler PF, Farr RS. Elevation of cord over maternal IgG immunoglobulin: evidence for an active placental IgG transport. Nature. (1966) 210:1070–71. 10.1038/2101070a0
    1. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. (2012) 2012:985646. 10.1155/2012/985646
    1. Schauer U, Stemberg F, Rieger CH, Büttner W, Borte M, Schubert S, et al. . Levels of antibodies specific to tetanus toxoid, Haemophilus influenzae type b, and pneumococcal capsular polysaccharide in healthy children and adults. Clin Diagn Lab Immunol. (2003) 10:202–7. 10.1128/CDLI.10.2.202-207.2003
    1. Malek A, Sager R, Schneider H. Maternal-fetal transport of immunoglobulin G and its subclasses during the third trimester of human pregnancy. Am J Reprod Immunol. (1994) 32:8–14. 10.1111/j.1600-0897.1994.tb00873.x
    1. Garty BZ, Ludomirsky A, Danon YL, Peter JB, Douglas SD. Placental transfer of immunoglobulin G subclasses. Clin Diagn Lab Immunol. (1994) 1:667–9. 10.1128/CDLI.1.6.667-669.1994
    1. Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. (2014) 5:520. 10.3389/fimmu.2014.00520
    1. Costa-Carvalho BT, Vieria HM, Dimantas RB, Arslanian C, Naspitz CK, Solé D, et al. . Transfer of IgG subclasses across placenta in term and preterm newborns. Braz J Med Biol Res. (1996) 29:201–4.
    1. Abu-Raya B, Kollmann TR, Marchant A, MacGillivray DM. The immune system of HIV-exposed uninfected infants. Front Immunol. (2016) 7:383. 10.3389/fimmu.2016.00383
    1. Dechavanne C, Cottrell G, Garcia A, Migot-Nabias F. Placental malaria: decreased transfer of maternal antibodies directed to Plasmodium falciparum and Impact on the incidence of febrile infections in infants. PLoS ONE. (2015) 10:e0145464. 10.1371/journal.pone.0145464
    1. Okoko BJ, Wesumperuma LH, Ota MO, Pinder M, Banya W, Gomez SF, et al. The influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental transfer of antibodies and IgG subclasses in a rural West African population. J Infect Dis. (2001) 184:627–32. 10.1086/322808
    1. Abu-Raya B, Edwards KM. Optimizing the timing of vaccine administration during pregnancy. JAMA. (2019) 321:935–6. 10.1001/jama.2019.0703
    1. Abu Raya B, Srugo I, Bamberger E. Optimal timing of immunization against pertussis during pregnancy. Clin Infect Dis. (2016) 63:143–4. 10.1093/cid/ciw233
    1. Louie JK, Acosta M, Jamieson DJ, Honein MA, the California Pandemic (H1N1) Working Group . Severe 2009 H1N1 influenza in pregnant and postpartum women in California. N Engl J Med. (2010) 362:27–35. 10.1056/NEJMoa0910444
    1. Principi N, Esposito S. Severe influenza in children: incidence and risk factors. Expert Rev Anti Infect Ther. (2016) 14:961–8. 10.1080/14787210.2016.1227701
    1. Principi N, Esposito S. Influenza vaccine use to protect healthy children: a debated topic. Vaccine. (2018) 36:5391–6. 10.1016/j.vaccine.2017.09.016
    1. Abu-Raya B, Bettinger JA, Vanderkooi OG, Vaudry W, Halperin SA, Sadarangani M, et al. . Burden of children hospitalized with pertussis in canada in the acellular pertussis vaccine era, 1999–2015. J Pediatr Infect Dis Soc. (2018) 9:118–27. 10.1093/jpids/piy128
    1. Abu-Raya B, Giles ML. Extending antenatal pertussis immunization to second trimester or at-birth pertussis immunization of premature infants? JAMA Pediatr. (2019) 173:294–5. 10.1001/jamapediatrics.2018.5139
    1. Riise Ø, Laake I, Vestrheim D, Flem E, Moster D, Riise Bergsaker MA, et al. . Risk of pertussis in relation to degree of prematurity in children less than 2 years of age. Pediatr Infect Dis J. (2017) 36:e151–6. 10.1097/INF.0000000000001545
    1. Centers for Disease Control and Prevention Vaccines and Preventable Diseases. Available online at: (accessed May 3, 2020).
    1. Tetanus Toxoid Vaccine Adsorbed. Available online at: (accessed May 3, 2020).
    1. Centers for Disease Control and Prevention Influenza (flu) Available online at: - anchor-star (accessed May 4, 2020).
    1. World Health Organization WHO Recommendation on Tetanus Toxoid Vaccination for Pregnant Women. (2018) Available online at: (accessed December 15, 2018).
    1. Stanfield JP, Gall D, Bracken PM. Single-dose antenatal tetanus immunisation. Lancet. (1973) 1:215–19. 10.1016/S0140-6736(73)90062-7
    1. Silveira CM, Cáceres VM, Dutra MG, Lopes-Camelo J, Castilla EE. Safety of tetanus toxoid in pregnant women: a hospital-based case-control study of congenital anomalies. Bull World Health Organ. (1995) 73:605–8.
    1. Sukumaran L, McCarthy NL, Kharbanda EO, McNeil MM, Naleway AL, Klein NP, et al. Association of Tdap vaccination with acute events and adverse birth outcomes among pregnant women with prior tetanus-containing immunizations. JAMA. (2015) 314:1581–7. 10.1001/jama.2015.12790
    1. Munoz FM, Bond NH, Maccato M, Pinell P, Hammill HA, Swamy GK, et al. . Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial. JAMA. (2014) 311:1760–9. 10.1001/jama.2014.3633
    1. Cumberland P, Shulman CE, Maple PA, Bulmer JN, Dorman EK, Kawuondo K, et al. . Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya. J Infect Dis. (2007) 196:550–7. 10.1086/519845
    1. Hood N, Chan MC, Maxwell SM, Familusi JB, Hart CA. Placental transfer of tetanus toxoid antibodies in Nigerian mothers. Ann Trop Paediatr. (1994) 14:179–82. 10.1080/02724936.1994.11747714
    1. Maertens K, Caboré RN, Huygen K, Hens N, Van Damme P, Leuridan E. Pertussis vaccination during pregnancy in Belgium: results of a prospective controlled cohort study. Vaccine. (2016) 34:142–50. 10.1016/j.vaccine.2015.10.100
    1. Kim JS, Kim SJ, Shin KJ, Hwang PH, Cho SC. Changes of tetanus specific IgG, IgM and IgG subclasses after DPT vaccination. Yonsei Med J. (1989) 30:158–63. 10.3349/ymj.1989.30.2.158
    1. World Health Organization The Immunological Basis for Immunization Series: Module 3: Tetanus. World Health Organization (2018). Available online at: (accessed July 1, 2019).
    1. Hoang HT, Leuridan E, Maertens K, Nguyen TD, Hens N, Vu NH, et al. . Pertussis vaccination during pregnancy in Vietnam: results of a randomized controlled trial Pertussis vaccination during pregnancy. Vaccine. (2016) 34:151–9. 10.1016/j.vaccine.2015.10.098
    1. UNICEF Elimination of Maternal and Neonatal Tetanus. Available at: (accessed December 15, 2018).
    1. World Health Organization Protecting All Against Tetanus. Available online at: (accessed November 24, 2019).
    1. Vygen-Bonnet S, Hellenbrand W, Garbe E, von Kries R, Bogdan C, Heininger U, et al. . Safety and effectiveness of acellular pertussis vaccination during pregnancy: a systematic review. BMC Infect Dis. (2020) 20:136. 10.1186/s12879-020-4824-3
    1. Donegan K, King B, Bryan P. Safety of pertussis vaccination in pregnant women in UK: observational study. BMJ. (2014) 349:g4219. 10.1136/bmj.g4219
    1. Kharbanda EO, Vazquez-Benitez G, Lipkind HS, Klein NP, Cheetham TC, Naleway A, et al. . Evaluation of the association of maternal pertussis vaccination with obstetric events and birth outcomes. JAMA. (2014) 312:1897–904. 10.1001/jama.2014.14825
    1. Kharbanda EO, Vazquez-Benitez G, Lipkind HS, Klein NP, Cheetham TC, Naleway AL, et al. . Maternal Tdap vaccination: coverage and acute safety outcomes in the vaccine safety datalink, 2007–2013. Vaccine. (2016) 34:968–73. 10.1016/j.vaccine.2015.12.046
    1. Morgan JL, Baggari SR, McIntire DD, Sheffield JS. Pregnancy outcomes after antepartum tetanus, diphtheria, and acellular pertussis vaccination. Obstet Gynecol. (2015) 125:1433–8. 10.1097/AOG.0000000000000862
    1. Shakib JH, Korgenski K, Sheng X, Varner MW, Pavia AT, Byington CL. Tetanus, diphtheria, acellular pertussis vaccine during pregnancy: pregnancy and infant health outcomes. J Pediatr. (2013) 163:1422–6.e1421-4. 10.1016/j.jpeds.2013.06.021
    1. Walls T, Graham P, Petousis-Harris H, Hill L, Austin N. Infant outcomes after exposure to Tdap vaccine in pregnancy: an observational study. BMJ Open. (2016) 6:e009536. 10.1136/bmjopen-2015-009536
    1. Villarreal Perez JZ, Aranda JMR, de la O, Cavazos M, Zamudio Osuna MJ, Dávila JM, Elizondo MRB, et al. . Randomized clinical trial of the safety and immunogenicity of the Tdap vaccine in pregnant Mexican women. Human Vaccines Immunother. (2017) 13:128–35. 10.1080/21645515.2016.1232786
    1. Berenson AB, Hirth JM, Rahman M, Laz TH, Rupp RE, Sarpong KO. Maternal and infant outcomes among women vaccinated against pertussis during pregnancy. Hum Vaccin Immunother. (2016) 12:1965–71. 10.1080/21645515.2016.1157241
    1. DeSilva M, Vazquez-Benitez G, Nordin JD, Lipkind HS, Romitti PA, DeStefano F, et al. . Tdap vaccination during pregnancy and microcephaly and other structural birth defects in offspring. JAMA. (2016) 316:1823–5. 10.1001/jama.2016.14432
    1. D'Heilly C, Switzer C, Macina D. Safety of maternal immunization against pertussis: a systematic review. Infect Dis Ther. (2019) 8:543–68. 10.1007/s40121-019-00265-6
    1. Datwani H, Moro PL, Harrington T, Broder KR. Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System. Vaccine. (2015) 33:3110–13. 10.1016/j.vaccine.2015.04.097
    1. Layton JB, Butler AM, Li D, Boggess KA, Weber DJ, McGrath LJ, et al. . Prenatal Tdap immunization and risk of maternal and newborn adverse events. Vaccine. (2017) 35:4072–8. 10.1016/j.vaccine.2017.06.071
    1. Halperin BA, Morris A, Mackinnon-Cameron D, Mutch J, Langley JM, McNeil SA, et al. . Kinetics of the antibody response to tetanus-diphtheria-acellular pertussis vaccine in women of childbearing age and postpartum women. Clin Infect Dis. (2011) 53:885–92. 10.1093/cid/cir538
    1. Abu Raya B, Srugo I, Kessel A, Peterman M, Vaknin A, Bamberger E. The decline of pertussis-specific antibodies after tetanus, diphtheria, and acellular pertussis immunization in late pregnancy. J Infect Dis. (2015) 212:1869–73. 10.1093/infdis/jiv324
    1. Maertens K, Tran TMP, Hens N, Van Damme P, Leuridan E. Effect of Prepregnancy pertussis vaccination in young infants. J Infect Dis. (2017) 215:1855–61. 10.1093/infdis/jix176
    1. Giammanco A, Taormina S, Chiarini A, Dardanoni G, Stefanelli P, Salmaso S, et al. Analogous IgG subclass response to pertussis toxin in vaccinated children, healthy or affected by whooping cough. Vaccine. (2003) 21:1924–31. 10.1016/S0264-410X(02)00823-X
    1. Hendrikx LH, Schure RM, Oztürk K, de Rond LG, de Greeff SC, Sanders EA, et al. . Different IgG-subclass distributions after whole-cell and acellular pertussis infant primary vaccinations in healthy and pertussis infected children. Vaccine. (2011) 29:6874–80. 10.1016/j.vaccine.2011.07.055
    1. Halperin SA, Langley JM, Ye LD, Elsherif M, Allen VM, Smith B, et al. . A Randomized controlled trial of the safety and immunogenicity of tetanus, diphtheria, acellular pertussis vaccine immunization during pregnancy and subsequent infant immune response. Clin Infect Dis. (2018) 67:1063–71. 10.1093/cid/ciy244
    1. Scanlon K, Skerry C, Carbonetti N. Association of pertussis toxin with severe pertussis disease. Toxins. (2019) 11:373. 10.3390/toxins11070373
    1. Nguyen AW, Wagner EK, Laber JR, Goodfield LL, Smallridge WE, Harvill ET, et al. . A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough. Sci Transl Med. (2015) 7:316ra195. 10.1126/scitranslmed.aad0966
    1. Kapil P, Papin JF, Wolf RF, Zimmerman LI, Wagner LD, Merkel TJ. Maternal vaccination with a monocomponent pertussis toxoid vaccine is sufficient to protect infants in a baboon model of whooping cough. J Infect Dis. (2018) 217:1231–6. 10.1093/infdis/jiy022
    1. Storsaeter J, Hallander HO, Gustafsson L, Olin P. Low levels of antipertussis antibodies plus lack of history of pertussis correlate with susceptibility after household exposure to Bordetella pertussis. Vaccine. (2003) 21:3542–9. 10.1016/S0264-410X(03)00407-9
    1. Wanlapakorn N, Maertens K, Chaithongwongwatthana S, Srimuan D, Suratannon N, Vongpunsawad S, et al. . Assessing the reactogenicity of Tdap vaccine administered during pregnancy and antibodies to Bordetella pertussis antigens in maternal and cord sera of Thai women. Vaccine. (2018) 36:1453–9. 10.1016/j.vaccine.2018.01.059
    1. Abu Raya B, Srugo I, Kessel A, Peterman M, Bader D, Gonen R, et al. The effect of timing of maternal tetanus, diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels - a prospective study. Vaccine. (2014) 32:5787–93. 10.1016/j.vaccine.2014.08.038
    1. Naidu MA, Muljadi R, Davies-Tuck ML, Wallace EM, Giles ML. The optimal gestation for pertussis vaccination during pregnancy: a prospective cohort study. Am J Obstet Gynecol. (2016) 215:237.e231-6. 10.1016/j.ajog.2016.03.002
    1. Healy CM, Rench MA, Swaim LS, Smith EO, Sangi-Haghpeykar H, Mathis MH, et al. . Association between third-trimester tdap immunization and neonatal pertussis antibody concentration. JAMA. (2018) 320:1464–70. 10.1001/jama.2018.14298
    1. Eberhardt CS, Blanchard-Rohner G, Lemaitre B, Boukrid M, Combescure C, Othenin-Girard V, et al. . Maternal immunization earlier in pregnancy maximizes antibody transfer and expected infant seropositivity against pertussis. Clin Infect Dis. (2016) 62:829–36. 10.1093/cid/ciw027
    1. Eberhardt CS, Blanchard-Rohner G, Lemaître B, Combescure C, Othenin-Girard V, Chilin A, et al. . Pertussis antibody transfer to preterm neonates after second- versus third-trimester maternal immunization. Clin Infect Dis. (2017) 64:1129–32. 10.1093/cid/cix046
    1. Abu Raya B, Bamberger E, Almog M, Peri R, Srugo I, Kessel A. Immunization of pregnant women against pertussis: the effect of timing on antibody avidity. Vaccine. (2015) 33:1948–52. 10.1016/j.vaccine.2015.02.059
    1. Abu-Raya B, Giles ML, Kollmann TR, Sadarangani M. The effect of timing of tetanus-diphtheria-acellular pertussis vaccine administration in pregnancy on the avidity of pertussis antibodies. Front Immunol. (2019) 10:2423. 10.3389/fimmu.2019.02423
    1. Maertens K, Hoang THT, Caboré RN, Leuridan E. Avidity of maternal pertussis antibodies after vaccination during pregnancy. Vaccine. (2015) 33:5489. 10.1016/j.vaccine.2015.05.075
    1. Dabrera G, Amirthalingam G, Andrews N, Campbell H, Ribeiro S, Kara E, 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) 60:333–7. 10.1093/cid/ciu821
    1. Winter K, Cherry JD, Harriman K. Effectiveness of prenatal tetanus, diphtheria, and acellular pertussis vaccination on pertussis severity in infants. Clin Infect Dis. (2017) 64:9–14. 10.1093/cid/ciw633
    1. Winter K, Nickell S, Powell M, Harriman K. Effectiveness of prenatal versus postpartum tetanus, diphtheria, and acellular pertussis vaccination in preventing infant pertussis. Clin Infect Dis. (2017) 64:3–8. 10.1093/cid/ciw634
    1. Bellido-Blasco J, Guiral-Rodrigo S, Míguez-Santiyán A, Salazar-Cifre A, González-Morán F. A case-control study to assess the effectiveness of pertussis vaccination during pregnancy on newborns, Valencian community, Spain, 1 March 2015 to 29 February 2016. Euro Surveill. (2017) 22:30545. 10.2807/1560-7917.ES.2017.22.22.30545
    1. Saul N, Wang K, Bag S, Baldwin H, Alexander K, Chandra M, et al. . Effectiveness of maternal pertussis vaccination in preventing infection and disease in infants: the NSW Public Health Network case-control study. Vaccine. (2018) 36:1887–92. 10.1016/j.vaccine.2018.02.047
    1. Fernandes EG, Sato APS, Vaz-de-Lima LRA, Rodrigues M, Leite D, de Brito CA, et al. The effectiveness of maternal pertussis vaccination in protecting newborn infants in Brazil: a case-control study. Vaccine. (2019) 37:5481–4. 10.1016/j.vaccine.2019.03.049
    1. Trotta F, Da Cas R, Spila Alegiani S, Gramegna M, Venegoni M, Zocchetti C, et al. . Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort study. BMJ. (2014) 348:g3361. 10.1136/bmj.g3361
    1. Nordin JD, Kharbanda EO, Vazquez Benitez G, Lipkind H, Vellozzi C, Destefano F, et al. Maternal influenza vaccine and risks for preterm or small for gestational age birth. J Pediatr. (2014) 164:1051–7.e1052. 10.1016/j.jpeds.2014.01.037
    1. Chambers CD, Johnson D, Xu R, Luo Y, Louik C, Mitchell AA, et al. . Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants. Vaccine. (2013) 31:5026–32. 10.1016/j.vaccine.2013.08.097
    1. Richards JL, Hansen C, Bredfeldt C, Bednarczyk RA, Steinhoff MC, Adjaye-Gbewonyo D, et al. . Neonatal outcomes after antenatal influenza immunization during the 2009 H1N1 influenza pandemic: impact on preterm birth, birth weight, and small for gestational age birth. Clin Infect Dis. (2013) 56:1216–22. 10.1093/cid/cit045
    1. Omer SB, Goodman D, Steinhoff MC, Rochat R, Klugman KP, Stoll BJ, et al. . Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study. PLoS Med. (2011) 8:e1000441. 10.1371/journal.pmed.1000441
    1. Vesikari T, Virta M, Heinonen S, Eymin C, Lavis N, Chabanon AL, et al. . Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in pregnant women: a randomized, observer-blind trial. Hum Vaccin Immunother. (2019) 16:623–9. 10.1080/21645515.2019.1667202
    1. Ortiz JR, Englund JA, Neuzil KM. Influenza vaccine for pregnant women in resource-constrained countries: a review of the evidence to inform policy decisions. Vaccine. (2011) 29:4439–52. 10.1016/j.vaccine.2011.04.048
    1. Ludvigsson JF, Zugna D, Cnattingius S, Richiardi L, Ekbom A, Örtqvist Å, et al. . Influenza H1N1 vaccination and adverse pregnancy outcome. Eur J Epidemiol. (2013) 28:579–88. 10.1007/s10654-013-9813-z
    1. Rubinstein F, Micone P, Bonotti A, Wainer V, Schwarcz A, Augustovski F, et al. . Influenza A/H1N1 MF59 adjuvanted vaccine in pregnant women and adverse perinatal outcomes: multicentre study. BMJ. (2013) 346:f393. 10.1136/bmj.f393
    1. Bratton KN, Wardle MT, Orenstein WA, Omer SB. Maternal influenza immunization and birth outcomes of stillbirth and spontaneous abortion: a systematic review and meta-analysis. Clin Infect Dis. (2015) 60:e11–19. 10.1093/cid/ciu915
    1. Donahue JG, Kieke BA, King JP, DeStefano F, Mascola MA, Irving SA, et al. . Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010–11 and 2011–12. Vaccine. (2017) 35:5314–22. 10.1016/j.vaccine.2017.06.069
    1. Madhi SA, Cutland CL, Kuwanda L, Weinberg A, Hugo A, Jones S, et al. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med. (2014) 371:918–31. 10.1056/NEJMoa1401480
    1. Tapia MD, Sow SO, Tamboura B, Tégueté I, Pasetti MF, Kodio M, et al. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial. Lancet Infect Dis. (2016) 16:1026–35. 10.1016/S1473-3099(16)30054-8
    1. Steinhoff MC, Katz J, Englund JA, Khatry SK, Shrestha L, Kuypers J, et al. . Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. Lancet Infect Dis. (2017) 17:981–9. 10.1016/S1473-3099(17)30252-9
    1. McMillan M, Porritt K, Kralik D, Costi L, Marshall H. Influenza vaccination during pregnancy: a systematic review of fetal death, spontaneous abortion, and congenital malformation safety outcomes. Vaccine. (2015) 33:2108–17. 10.1016/j.vaccine.2015.02.068
    1. Giles ML, Krishnaswamy S, Macartney K, Cheng A. The safety of inactivated influenza vaccines in pregnancy for birth outcomes: a systematic review. Hum Vaccin Immunother. (2019) 15:687–99. 10.1080/21645515.2018.1540807
    1. Ohfuji S, Deguchi M, Tachibana D, Koyama M, Takagi T, Yoshioka T, et al. . Safety of influenza vaccination on adverse birth outcomes among pregnant women: a prospective cohort study in Japan. Int J Infect Dis. (2020) 93:68–76. 10.1016/j.ijid.2020.01.033
    1. Donahue JG, Kieke BA, King JP, Mascola MA, Shimabukuro TT, DeStefano F, et al. . Inactivated influenza vaccine and spontaneous abortion in the Vaccine Safety Datalink in 2012–13:2013–14, and 2014–15. Vaccine. (2019) 37:6673–81. 10.1016/j.vaccine.2019.09.035
    1. Sukumaran L, McCarthy NL, Kharbanda EO, Weintraub ES, Vazquez-Benitez G, McNeil MM, et al. . Safety of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis and influenza vaccinations in pregnancy. Obstetr Gynecol. (2015) 126:1069–74. 10.1097/AOG.0000000000001066
    1. Frasca D, Diaz A, Romero M, Mendez NV, Landin AM, Blomberg BB. Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011–2012 influenza vaccine season. Immun Ageing. (2013) 10:14. 10.1186/1742-4933-10-14
    1. Jackson LA, Patel SM, Swamy GK, Frey SE, Creech CB, Munoz FM, et al. . Immunogenicity of an inactivated monovalent 2009 H1N1 influenza vaccine in pregnant women. J Infect Dis. (2011) 204:854–63. 10.1093/infdis/jir440
    1. Horner I, Nanan R, Liu A. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med. (2014) 371:2340. 10.1056/NEJMc1412050
    1. Nunes MC, Cutland CL, Dighero B, Bate J, Jones S, Hugo A, et al. . Kinetics of hemagglutination-inhibiting antibodies following maternal influenza vaccination among mothers with and those without HIV infection and their infants. J Infect Dis. (2015) 212:1976–87. 10.1093/infdis/jiv339
    1. Principi N, Senatore L, Esposito S. Protection of young children from influenza through universal vaccination. Hum Vaccin Immunother. (2015) 11:2350–8. 10.1080/21645515.2015.1055428
    1. Nunes MC, Cutland CL, Jones S, Hugo A, Madimabe R, Simoes EA, et al. . Duration of infant protection against influenza illness conferred by maternal immunization: secondary analysis of a randomized clinical trial. JAMA Pediatr. (2016) 170:840–7. 10.1001/jamapediatrics.2016.0921
    1. Zuccotti G, Pogliani L, Pariani E, Amendola A, Zanetti A. Transplacental antibody transfer following maternal immunization with a pandemic 2009 influenza A(H1N1) MF59-adjuvanted vaccine. JAMA. (2010) 304:2360–1. 10.1001/jama.2010.1729
    1. Black S, Nicolay U, Vesikari T, Knuf M, Del Giudice G, Della Cioppa G, et al. . Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr Infect Dis J. (2011) 30:1081–5. 10.1097/INF.0b013e3182367662
    1. Grohskopf LA, Alyanak E, Broder KR, Walter EB, Fry AM, Jernigan DB. Prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices - United States, 2019–20 Influenza Season. MMWR Recomm Rep. (2019) 68:1–21. 10.15585/mmwr.rr6803a1
    1. European Centre for Disease Prevention and Control Seasonal Influenza Vaccination and Antiviral Use in EU/EEA Member States – Overview of Vaccine Recommendations for 2017–2018 and Vaccination Coverage Rates for 2015–2016 and 2016–2017 Influenza Seasons. Stockholm: ECDC; (2018). Available online at: (accessed November 24, 2019).
    1. Sperling RS, Engel SM, Wallenstein S, Kraus TA, Garrido J, Singh T, et al. Immunogenicity of trivalent inactivated influenza vaccination received during pregnancy or postpartum. Obstet Gynecol. (2012) 119:631–9. 10.1097/AOG.0b013e318244ed20
    1. Blanchard-Rohner G, Meier S, Bel M, Combescure C, Othenin-Girard V, Swali RAB, et al. . Influenza vaccination given at least 2 weeks before delivery to pregnant women facilitates transmission of seroprotective influenza-specific antibodies to the newborn. Pediatr Infect Dis J. (2013) 32:1374–80. 10.1097/01.inf.0000437066.40840.c4
    1. Katz J, Englund JA, Steinhoff MC, Khatry SK, Shrestha L, Kuypers J, et al. . Impact of timing of influenza vaccination in pregnancy on transplacental antibody transfer, influenza incidence, and birth outcomes: a randomized trial in rural Nepal. Clin Infect Dis. (2018) 67:334–40. 10.1093/cid/ciy090
    1. Dodds L, McNeil SA, Fell DB, Allen VM, Coombs A, Scott J, et al. . Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. CMAJ. (2007) 176:463–8. 10.1503/cmaj.061435
    1. Vilca LM, Verma A, Bonati M, Campins M. Impact of influenza on outpatient visits and hospitalizations among pregnant women in Catalonia, Spain. J Infect. (2018) 77:553–60. 10.1016/j.jinf.2018.06.015
    1. Poehling KA, Edwards KM, Weinberg GA, Szilagyi P, Staat MA, Iwane MK, et al. . The underrecognized burden of influenza in young children. N Engl J Med. (2006) 355:31–40. 10.1056/NEJMoa054869
    1. Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, Glover MJ, et al. . Influenza-associated deaths among children in the United States, 2003–2004. N Engl J Med. (2005) 353:2559–67. 10.1056/NEJMoa051721
    1. Thompson MG, Li DK, Shifflett P, Sokolow LZ, Ferber JR, Kurosky S, et al. . Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010–2011 and 2011–2012 influenza seasons. Clin Infect Dis. (2014) 58:449–57. 10.1093/cid/cit750
    1. Omer SB, Richards JL, Madhi SA, Tapia MD, Steinhoff MC, Aqil AR, et al. . Three randomized trials of maternal influenza immunization in Mali, Nepal, and South Africa: methods and expectations. Vaccine. (2015) 33:3801–12. 10.1016/j.vaccine.2015.05.077
    1. Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson E, et al. . Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med. (2008) 359:1555–64. 10.1056/NEJMoa0708630
    1. Shakib JH, Korgenski K, Presson AP, Sheng X, Varner MW, Pavia AT, et al. . Influenza in infants born to women vaccinated during pregnancy. Pediatrics. (2016) 137:e20152360. 10.1542/peds.2015-2360
    1. Eick AA, Uyeki TM, Klimov A, Hall H, Reid R, Santosham M, et al. . Maternal influenza vaccination and effect on influenza virus infection in young infants. Arch Pediatr Adolesc Med. (2011) 165:104–11. 10.1001/archpediatrics.2010.192
    1. Dabrera G, Zhao H, Andrews N, Begum F, Green H, Ellis J, et al. . Effectiveness of seasonal influenza vaccination during pregnancy in preventing influenza infection in infants, England, 2013/14. Euro Surveill. (2014) 19:20959. 10.2807/1560-7917.ES2014.19.45.20959
    1. 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) 14:758–66. 10.1080/21645515.2017.1345385
    1. Omer SB, Clark DR, Aqil AR, Tapia MD, Nunes MC, Kozuki N, et al. . Maternal Influenza immunization and prevention of severe clinical pneumonia in young infants: analysis of randomized controlled trials conducted in Nepal, Mali and South Africa. Pediatr Infect Dis J. (2018) 37:436–40. 10.1097/INF.0000000000001914
    1. European Medicines Agency Quadrivalent Influenza Vaccine (Split virion, inactivated) (2020). Available online at: (accessed February 17, 2020).
    1. Giles ML, Cheng AC. Regulatory agencies have a role to play in maintaining consumer confidence in vaccine safety for pregnant women. Hum Vaccines Immunother. (2020). 10.1080/21645515.2020.1718976. [Epub ahead of print].
    1. Jones C, Pollock L, Barnett SM, Battersby A, Kampmann B. The relationship between concentration of specific antibody at birth and subsequent response to primary immunization. Vaccine. (2014) 32:996–1002. 10.1016/j.vaccine.2013.11.104
    1. Van Savage J, Decker MD, Edwards KM, Sell SH, Karzon DT. Natural history of pertussis antibody in the infant and effect on vaccine response. J Infect Dis. (1990) 161:487–92. 10.1093/infdis/161.3.487
    1. Niewiesk S. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front Immunol. (2014) 5:446. 10.3389/fimmu.2014.00446
    1. Englund JA, Glezen WP, Thompson C, Anwaruddin R, Turner CS, Siber GR. Haemophilus influenzae type b-specific antibody in infants after maternal immunization. Pediatr Infect Dis J. (1997) 16:1122–30. 10.1097/00006454-199712000-00005
    1. Nahm MH, Glezen P, Englund J. The influence of maternal immunization on light chain response to Haemophilus influenzae type b vaccine. Vaccine. (2003) 21:3393–7. 10.1016/S0264-410X(03)00340-2
    1. Ladhani SN, Andrews NJ, Southern J, Jones CE, Amirthalingam G, Waight PA, et al. . Antibody responses after primary immunization in infants born to women receiving a pertussis-containing vaccine during pregnancy: single arm observational study with a historical comparator. Clin Infect Dis. (2015) 61:1637–44. 10.1093/cid/civ695
    1. Maertens K, Cabore RN, Huygen K, Vermeiren S, Hens N, Van Damme P, et al. . Pertussis vaccination during pregnancy in Belgium: follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age. Vaccine. (2016) 34:3613–19. 10.1016/j.vaccine.2016.04.066
    1. Maertens K, Hoang TT, Nguyen TD, Cabore RN, Duong TH, Huygen K, et al. . The effect of maternal pertussis immunization on infant vaccine responses to a booster pertussis-containing vaccine in Vietnam. Clin Infect Dis. (2016) 63:S197–204. 10.1093/cid/ciw551
    1. Zimmermann P, Perrett KP, Messina NL, Donath S, Ritz N, van der Klis FRM, et al. . The effect of maternal immunisation during pregnancy on infant vaccine responses. EClin Med. (2019) 13:21–30. 10.1016/j.eclinm.2019.06.010
    1. Englund JA, Anderson EL, Reed GF, Decker MD, Edwards KM, Pichichero ME, et al. . The effect of maternal antibody on the serologic response and the incidence of adverse reactions after primary immunization with acellular and whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids. Pediatrics. (1995) 96:580–4.
    1. Ibrahim R, Ali SA, Kazi AM, Rizvi A, Guterman LB, Bednarczyk RA, et al. . Impact of maternally derived pertussis antibody titers on infant whole-cell pertussis vaccine response in a low income setting. Vaccine. (2018) 36:7048–53. 10.1016/j.vaccine.2018.09.045
    1. Wanlapakorn N, Maertens K, Vongpunsawad S, Peunpa J, Tran TMP, Hens N, et al. . Quantity and quality of antibodies after acellular versus whole cell pertussis vaccines in infants born to mothers who received Tdap during pregnancy: a randomised trial. Clin Infect Dis. (2019). 10.1093/cid/ciz778. [Epub ahead of print].
    1. Abu Raya B, Edwards KM. Interference with pertussis vaccination in infants after maternal pertussis vaccination. Pediatrics. (in press).
    1. Maertens K, Burbidge P, van Damme P, Goldblatt D, Leuridan E. Pneumococcal immune response in infants whose mothers received tdap vaccination during pregnancy. Pediatr Infect Dis J. (2017) 36:1186–92. 10.1097/INF.0000000000001601
    1. Heininger U. Is there a need for a stand-alone acellular pertussis vaccine? Pediatr Infect Dis J. (2018) 37:359–60. 10.1097/INF.0000000000001767
    1. Walter EB, Englund JA, Blatter M, Nyberg J, Ruben FL, Decker MD. Trivalent inactivated influenza virus vaccine given to two-month-old children: An off-season pilot study. Pediatr Infect Dis J. (2009) 28:1099–104. 10.1097/INF.0b013e3181b0c0ca
    1. Halasa NB, Gerber MA, Chen Q, Wright PF, Edwards KM. Safety and immunogenicity of trivalent inactivated influenza vaccine in infants. J Infect Dis. (2008) 197:1448–54. 10.1086/587643
    1. Siegrist CA. Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants. Vaccine. (2003) 21:3406–12. 10.1016/S0264-410X(03)00342-6
    1. Naniche D. Human immunology of measles virus infection. Curr Top Microbiol Immunol. (2009) 330:151–71. 10.1007/978-3-540-70617-5_8
    1. Kim D, Huey D, Oglesbee M, Niewiesk S. Insights into the regulatory mechanism controlling the inhibition of vaccine-induced seroconversion by maternal antibodies. Blood. (2011) 117:6143–51. 10.1182/blood-2010-11-320317
    1. Vono M, Eberhardt CS, Auderset F, Mastelic-Gavillet B, Lemeille S, Christensen D, et al. Maternal antibodies inhibit neonatal and infant responses to vaccination by shaping the early-life B cell repertoire within germinal centers. Cell Rep. (2019) 28:1773–84.e1775. 10.1016/j.celrep.2019.07.047
    1. Orije MRP, Maertens K, Corbière V, Wanlapakorn N, Van Damme P, Leuridan E, et al. The effect of maternal antibodies on the cellular immune response after infant vaccination: a review. Vaccine. (2020) 38:20–28. 10.1016/j.vaccine.2019.10.025
    1. Rastogi D, Wang C, Mao X, Lendor C, Rothman PB, Miller RL. Antigen-specific immune responses to influenza vaccine in utero. J Clin Invest. (2007) 117:1637–46. 10.1172/JCI29466
    1. Esposito S, Principi N. Strategies to develop vaccines of pediatric interest. Expert Rev Vaccines. (2017) 16:175–86. 10.1080/14760584.2017.1237875
    1. Charlier C, Beaudoin MC, Couderc T, Lortholary O, Lecuit M. Arboviruses and pregnancy: maternal, fetal, and neonatal effects. Lancet Child Adolesc Health. (2017) 1:134–46. 10.1016/S2352-4642(17)30021-4
    1. Carles G, Peiffer H, Talarmin A. Effects of dengue fever during pregnancy in French Guiana. Clin Infect Dis. (1999) 28:637–40. 10.1086/515144
    1. Kleber de Oliveira W, Cortez-Escalante J, De Oliveira WT, do Carmo GM, Henriques CM, et al. . Increase in reported prevalence of microcephaly in infants born to women living in areas with confirmed zika virus transmission during the first trimester of pregnancy - Brazil, 2015. MMWR Morb Mortal Wkly Rep. (2016) 65:242–7. 10.15585/mmwr.mm6509e2
    1. Abbink P, Stephenson KE, Barouch DH. Zika virus vaccines. Nat Rev Microbiol. (2018) 16:594–600. 10.1038/s41579-018-0039-7
    1. Thisyakorn U, Thisyakorn C. Latest developments and future directions in dengue vaccines. Ther Adv Vaccines. (2014) 2:3–9. 10.1177/2051013613507862
    1. Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH, Petit S, et al. . Epidemiology of invasive group B streptococcal disease in the United States, 1999–2005. JAMA. (2008) 299:2056–65. 10.1001/jama.299.17.2056
    1. Tapiainen T, Koivusaari P, Brinkac L, Lorenzi HA, Salo J, Renko M, et al. . Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants. Sci Rep. (2019) 9:10635. 10.1038/s41598-019-46964-5
    1. Di Renzo GC, Melin P, Berardi A, Blennow M, Carbonell-Estrany X, Donzelli GP, et al. . Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference. J Matern Fetal Neonatal Med. (2015) 28:766–82. 10.3109/14767058.2014.934804
    1. Seale AC, Baker CJ, Berkley JA, Madhi SA, Ordi J, Saha SK, et al. . Vaccines for maternal immunization against Group B Streptococcus disease: WHO perspectives on case ascertainment and case definitions. Vaccine. (2019) 37:4877–85. 10.1016/j.vaccine.2019.07.012
    1. Dzanibe S, Madhi SA. Systematic review of the clinical development of group B streptococcus serotype-specific capsular polysaccharide-based vaccines. Expert Rev Vaccines. (2018) 17:635–51. 10.1080/14760584.2018.1496021
    1. Madrid L, Seale AC, Kohli-Lynch M, Edmond KM, Lawn JE, Heath PT, et al. . Infant Group B streptococcal disease incidence and serotypes worldwide: systematic review and meta-analyses. Clin Infect Dis. (2017) 65:S160–72. 10.1093/cid/cix656
    1. Shabayek S, Spellerberg B. Group B Streptococcal Colonization, Molecular Characteristics, and Epidemiology. Front Microbiol. (2018) 9:437. 10.3389/fmicb.2018.00437
    1. Song JY, Lim JH, Lim S, Yong Z, Seo HS. Progress toward a group B streptococcal vaccine. Hum Vaccin Immunother. (2018) 14:2669–81. 10.1080/21645515.2018.1493326
    1. Le Doare K, Kampmann B, Vekemans J, Heath PT, Goldblatt D, Nahm MH, et al. . Serocorrelates of protection against infant group B streptococcus disease. Lancet Infect Dis. (2019) 19:e162–71. 10.1016/S1473-3099(18)30659-5
    1. Heyderman RS, Madhi SA, French N, Cutland C, Ngwira B, Kayambo D, et al. . Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. Lancet Infect Dis. (2016) 16:546–55. 10.1016/S1473-3099(15)00484-3
    1. Fabbrini M, Rigat F, Tuscano G, Chiarot E, Donders G, Devlieger R, et al. . Functional activity of maternal and cord antibodies elicited by an investigational group B Streptococcus trivalent glycoconjugate vaccine in pregnant women. J Infect. (2018) 76:449–56. 10.1016/j.jinf.2018.01.006
    1. Madhi SA, Cutland CL, Jose L, Koen A, Govender N, Wittke F, et al. . Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in healthy women and their infants: a randomised phase 1b/2 trial. Lancet Infect Dis. (2016) 16:923–34. 10.1016/S1473-3099(16)00152-3
    1. Madhi SA, Koen A, Cutland CL, Jose L, Govender N, Wittke F, et al. . Antibody kinetics and response to routine vaccinations in infants born to women who received an investigational trivalent group B streptococcus polysaccharide CRM197-conjugate vaccine during pregnancy. Clin Infect Dis. (2017) 65:1897–904. 10.1093/cid/cix666
    1. Shi T, McAllister DA, O'Brien KL, Simoes EAF, Madhi SA, Gessner BD, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. (2017) 390:946–58. 10.1016/S0140-6736(17)30938-8
    1. Baraldi E, Lanari M, Manzoni P, Rossi GA, Vandini S, Rimini A, et al. . Inter-society consensus document on treatment and prevention of bronchiolitis in newborns and infants. Ital J Pediatr. (2014) 40:65. 10.1186/1824-7288-40-65
    1. Borchers AT, Chang C, Gershwin ME, Gershwin LJ. Respiratory syncytial virus–a comprehensive review. Clin Rev Allergy Immunol. (2013) 45:331–79. 10.1007/s12016-013-8368-9
    1. Resch B. Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection. Hum Vaccin Immunother. (2017) 13:2138–49. 10.1080/21645515.2017.1337614
    1. Wegzyn C, Toh LK, Notario G, Biguenet S, Unnebrink K, Park C, et al. . Safety and effectiveness of palivizumab in children at high risk of serious disease due to respiratory syncytial virus infection: a systematic review. Infect Dis Ther. (2014) 3:133–58. 10.1007/s40121-014-0046-6
    1. Robbie GJ, Criste R, Dall'acqua WF, Jensen K, Patel NK, Losonsky GA, et al. . A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. (2013) 57:6147–53. 10.1128/AAC.01285-13
    1. Gerretsen HE, Sande CJ. Development of respiratory syncytial virus (RSV) vaccines for infants. J Infect. (2017) 74(Suppl. 1):S143–6. 10.1016/S0163-4453(17)30205-0
    1. August A, Glenn GM, Kpamegan E, Hickman SP, Jani D, Lu H, et al. . A Phase 2 randomized, observer-blind, placebo-controlled, dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus F particle vaccine formulations in healthy women of childbearing age. Vaccine. (2017) 35:3749–59. 10.1016/j.vaccine.2017.05.045
    1. Munoz FM, Swamy GK, Hickman SP, Agrawal S, Piedra PA, Glenn GM, et al. . Safety and immunogenicity of a respiratory syncytial virus fusion (F) protein nanoparticle vaccine in healthy third-trimester pregnant women and their infants. J Infect Dis. (2019) 220:1802–15. 10.1093/infdis/jiz390
    1. Chu HY, Tielsch J, Katz J, Magaret AS, Khatry S, LeClerq SC, et al. . Transplacental transfer of maternal respiratory syncytial virus (RSV) antibody and protection against RSV disease in infants in rural Nepal. J Clin Virol. (2017) 95:90–95. 10.1016/j.jcv.2017.08.017
    1. Glezen WP, Paredes A, Allison JE, Taber LH, Frank AL. Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level. J Pediatr. (1981) 98:708–15. 10.1016/S0022-3476(81)80829-3
    1. Nyiro JU, Sande CJ, Mutunga M, Kiyuka PK, Munywoki PK, Scott JA, et al. . Absence of association between cord specific antibody levels and severe Respiratory Syncytial Virus (RSV) disease in early infants: a case control study from coastal Kenya. PLoS ONE. (2016) 11:e0166706. 10.1371/journal.pone.0166706
    1. Muñoz F, Madhi S, Swamy GK, Heath PT, Vrbicky K, Glenn G, et al. Phase 3 PREPARE study: efficacy and safety of an RSV vaccine administered to pregnant women for the prevention of RSV lower respiratory tract infection in infants. In: 37 Annual Meeting of the European Society for Pediatric Infectious Diseases. Ljubljana (2019).
    1. Maertens K, De Schutter S, Braeckman T, Baerts L, Van Damme P, De Meester I, et al. . Breastfeeding after maternal immunisation during pregnancy: providing immunological protection to the newborn: a review. Vaccine. (2014) 32:1786–92. 10.1016/j.vaccine.2014.01.083
    1. Abu Raya B, Srugo I, Kessel A, Peterman M, Bader D, Peri R, et al. . The induction of breast milk pertussis specific antibodies following gestational tetanus-diphtheria-acellular pertussis vaccination. Vaccine. (2014) 32:5632–7. 10.1016/j.vaccine.2014.08.006
    1. De Schutter S, Maertens K, Baerts L, De Meester I, Van Damme P, Leuridan E. Quantification of vaccine-induced antipertussis toxin secretory IgA antibodies in breast milk: comparison of different vaccination strategies in women. Pediatr Infect Dis J. (2015) 34:e149–52. 10.1097/INF.0000000000000675
    1. Schlaudecker EP, Steinhoff MC, Omer SB, McNeal MM, Roy E, Arifeen SE, et al. . IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization. PLoS ONE. (2013) 8:e70867. 10.1371/journal.pone.0070867
    1. Dangor Z, Khan M, Kwatra G, Izu A, Nakwa F, Ramdin T, et al. . The association between breastmilk group B Streptococcal capsular antibody levels and late-onset disease in young infants. Clin Infect Dis. (2019) 70: 1110–14. 10.1093/cid/ciz360
    1. Mazur NI, Horsley NM, Englund JA, Nederend M, Magaret A, Kumar A, et al. . Breast milk prefusion F immunoglobulin G as a correlate of protection against respiratory syncytial virus acute respiratory illness. J Infect Dis. (2019) 219:59–67. 10.1093/infdis/jiy477
    1. World Health Organization Maternal and Neonatal Tetanus Elimination by 2005: Strategies for Achieving and Maintaining Elimination. Geneva: WHO; (2000). Available online at: (accessed December 15, 2018).
    1. Esposito S, Tremolati E, Bellasio M, Chiarelli G, Marchisio P, Tiso B, et al. . Attitudes and knowledge regarding influenza vaccination among hospital health workers caring for women and children. Vaccine. (2007) 25:5283–9. 10.1016/j.vaccine.2007.05.011
    1. Mak TK, Mangtani P, Leese J, Watson JM, Pfeifer D. Influenza vaccination in pregnancy: current evidence and selected national policies. Lancet Infect Dis. (2008) 8:44–52. 10.1016/S1473-3099(07)70311-0
    1. Centers for Disease Control and Prevention (CDC) . Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women and persons who have or anticipate having close contact with an infant aged <12 months — Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. (2011) 60:1424–6.
    1. Kahn KE, Black CL, Ding H, Williams WW, Lu PJ, Fiebelkorn AP, et al. . Influenza and Tdap vaccination coverage among pregnant women - United States, April 2018. MMWR Morb Mortal Wkly Rep. (2018) 67:1055–9. 10.15585/mmwr.mm6738a3
    1. Public Health England Pertussis Vaccination Programme for Pregnant Women Update: Vaccine Coverage in England, April to June 2018. Health Protection Report, Vol. 12.
    1. World Health Organizaion WHO Europe/ECDC joint statement: Low Uptake of Seasonal Influenza Vaccination in Europe May Jeopardize Capacity to Protect People in Next Pandemic. Available online at: (accessed December 15, 2018).
    1. Descamps A, Launay O, Bonnet C, Blondel B. Seasonal influenza vaccine uptake and vaccine refusal among pregnant women in France: results from a national survey. Hum Vaccin Immunother. (2019) 16:1093–100. 10.1080/21645515.2019.1688035
    1. Erb ML, Erlanger TE, Heininger U. Child-parent immunization survey: how well are national immunization recommendations accepted by the target groups? Vaccine X. (2019) 1:100013. 10.1016/j.jvacx.2019.100013
    1. Lutz CS, Carr W, Cohn A, Rodriguez L. Understanding barriers and predictors of maternal immunization: identifying gaps through an exploratory literature review. Vaccine. (2018) 36:7445–55. 10.1016/j.vaccine.2018.10.046
    1. Shavell VI, Moniz MH, Gonik B, Beigi RH. Influenza immunization in pregnancy: overcoming patient and health care provider barriers. Am J Obstet Gynecol. (2012) 207:S67–74. 10.1016/j.ajog.2012.06.077
    1. Broughton DE, Beigi RH, Switzer GE, Raker CA, Anderson BL. Obstetric health care workers' attitudes and beliefs regarding influenza vaccination in pregnancy. Obstet Gynecol. (2009) 114:981–7. 10.1097/AOG.0b013e3181bd89c2
    1. Leddy MA, Anderson BL, Power ML, Gall S, Gonik B, Schulkin J. Changes in and current status of obstetrician-gynecologists' knowledge, attitudes, practice regarding immunization. Obstet Gynecol Surv. (2009) 64:823–9. 10.1097/OGX.0b013e3181c4bbb7
    1. Power ML, Leddy MA, Anderson BL, Gall SA, Gonik B, Schulkin J. Obstetrician-gynecologists' practices and perceived knowledge regarding immunization. Am J Prev Med. (2009) 37:231–4. 10.1016/j.amepre.2009.05.019
    1. Vilca LM, Martínez C, Burballa M, Campins M. Maternal care providers' barriers regarding influenza and pertussis vaccination during pregnancy in Catalonia, Spain. Matern Child Health J. (2018) 22:1016–24. 10.1007/s10995-018-2481-6
    1. Beigi RH, Fortner KB, Munoz FM, Roberts J, Gordon JL, Han HH, et al. . Maternal immunization: opportunities for scientific advancement. Clin Infect Dis. (2014) 59(Suppl. 7):S408–14. 10.1093/cid/ciu708
    1. Frew PM, Kriss JL, Chamberlain AT, Malik F, Chung Y, Cortés M, et al. . A randomized trial of maternal influenza immunization decision-making: a test of persuasive messaging models. Hum Vaccin Immunother. (2016) 12:1989–96. 10.1080/21645515.2016.1199309
    1. Goodman K, Mossad SB, Taksler GB, Emery J, Schramm S, Rothberg MB. Impact of video education on influenza vaccination in pregnancy. J Reprod Med. (2015) 60:471–9.
    1. Kriss JL, Frew PM, Cortes M, Malik FA, Chamberlain AT, Seib K, et al. . Evaluation of two vaccine education interventions to improve pertussis vaccination among pregnant African American women: a randomized controlled trial. Vaccine. (2017) 35:1551–8. 10.1016/j.vaccine.2017.01.037
    1. Meharry PM, Cusson RM, Stiller R, Vázquez M. Maternal influenza vaccination: evaluation of a patient-centered pamphlet designed to increase uptake in pregnancy. Matern Child Health J. (2014) 18:1205–14. 10.1007/s10995-013-1352-4
    1. Panda B, Stiller R, Panda A. Influenza vaccination during pregnancy and factors for lacking compliance with current CDC guidelines. J Matern Fetal Neonatal Med. (2011) 24:402–6. 10.3109/14767058.2010.497882
    1. Ledent E, Gabutti G, de Bekker-Grob EW, Alcázar Zambrano JL, Campins Martí M, Del Hierro Gurruchaga MT, et al. . Attributes influencing parental decision-making to receive the Tdap vaccine to reduce the risk of pertussis transmission to their newborn - outcome of a cross-sectional conjoint experiment in Spain and Italy. Hum Vaccin Immunother. (2019) 15:1080–91. 10.1080/21645515.2019.1571890
    1. Vilca LM, Esposito S. The crucial role of maternal care providers as vaccinators for pregnant women. Vaccine. (2018) 36:5379–84. 10.1016/j.vaccine.2017.08.017
    1. Chamberlain AT, Berkelman RL, Ault KA, Rosenberg ES, Orenstein WA, Omer SB. Trends in reasons for non-receipt of influenza vaccination during pregnancy in Georgia, 2004–2011. Vaccine. (2016) 34:1597–603. 10.1016/j.vaccine.2016.01.058
    1. Danchin MH, Costa-Pinto J, Attwell K, Willaby H, Wiley K, Hoq M, et al. . Vaccine decision-making begins in pregnancy: correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake. Vaccine. (2018) 36:6473–9. 10.1016/j.vaccine.2017.08.003
    1. Benova L, Tunçalp Ö, Moran AC, Campbell OMR. Not just a number: examining coverage and content of antenatal care in low-income and middle-income countries. BMJ Glob Health. (2018) 3:e000779. 10.1136/bmjgh-2018-000779

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