Maternal immunization

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Vaccination Main Page

Maternal immunization

Overview

Immunology

Recommendations

Future Perspective

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]

Overview

Immunization prevents illness, disability, and death from vaccine-preventable diseases. Vaccines are useful in reducing childhood mortality and morbidity. The standard vaccination schedule starts at early infancy and is not complete by the age of 6 months. Therefore, most children do not have immunological protection during the period of early infancy, which may predispose them to infections. This gap may result in higher infection-related hospitalization and disease complications in early infancy than in older children. Maternal vaccination has entered consideration as a potential means of closing this gap. While maternal vaccination can protect an expectant mother from acquiring infection, it is also effective for infant protection.

Immunology

Maternal immunity changes during pregnancy, under influence of pregnancy-associated hormonal changes. Increased levels of estrogen and progesterone are the most important factors for these changes. Increased levels of estradiol are associated with increased levels of the body's T-helper type 2 cell response, compared to type 1 T-cells.[1][2] However, increased levels of progesterone may result in a decrease in the robustness of the immune response and an alteration in the function of the immune system.[3][4] Other aspects of the immune response, such as phagocytosis and the number of neutrophils and monocytes, remain unchanged.[4] These changes (alterations in cell-mediated immunity) are to blame for sub-optimal immune responses to certain viral infections (e.g., influenza). Furthermore, this accounts for the need for immunization against these infections in pregnant women.[5] Other pathways within the immune system remain intact during pregnancy; immunosuppression does not occur as a result of pregnancy. The clinical effectiveness of vaccination during pregnancy is maintained, as changes in the immune balance do not influence their effectiveness.[6][7][8]

Maternal immunization recommendation

Inactivated influenza and combined tetanus-diphteria-acellular pertussis (TDaP) vaccines are recommended for pregnant women in the U.S. Hepatitis B and hepatitis E vaccines are recommended in some other countries.

The following table summarizes available vaccines and current recommendations for their administration during pregnancy.

Vaccine Type Recommendation for pregnant women Specific consideration
Category Comment
Anthrax Inactivated May be used in women with high risk of exposure; not recommended for those with low risk of exposure. Travel and other Generally, inactivated vaccines are safe in pregnancy, but the anthrax vaccine is reserved for high-risk mothers only.
BCG Live Contraindicated Travel and other Live vaccines are contraindicated in pregnancy; however, there is no evidence to suggest that BCG contributes to adverse effects in pregnancy.
HAV Inactivated Recommended for specific indications Routine Indications:
  • History of injection or non-injection recreational drug use
  • Work with HAV-infected primates
  • Work with HAV in a research laboratory
  • Chronic liver disease
  • Receiving clotting factor concentrates
  • Travel to or work in countries with high or intermediate endemicity of hepatitis A
HBV Recombinant Recommended for specific indications Routine Indications:
  • Having had an HBsAg-positive sexual partner
  • Having had more than one sex partner during the previous 6 months
  • Having been evaluated or treated for an STD
  • History of recent or current IV drug use

The recommended schedule is 0, 1, and 6 months.

HPV Inactivated Not recommended Routine If a woman is found to be pregnant during the administration of an HPV series, the remaining doses should be delayed until after pregnancy is completed.
Influenza Inactivated Recommended Routine Recommended for all women who are or will be pregnant during influenza season.
Live, attenuated Contraindicated Routine Risk of fetal infection
Japanese encephalitis virus Inactivated Inadequate data for specific recommendation Travel and other Theoretical risk for fetus; however, it is recommended for pregnant women traveling to high-risk areas.
Meningococcal Inactivated
  • Serotype ACWY conjugate vaccine may be used in the case of a specific indication
  • Serotype B vaccine administration should be based on a risk–benefit assessment for the patient
 Routine
MMR Live Contraindicated Routine Live vaccines are contraindicated during pregnancy.

If the vaccine is inadvertently given to a pregnant woman, she should be informed of the theoretical risks to the fetus. However, receipt of the vaccine is not an indication for termination of pregnancy.

Pneumococcal Conjugate

(PCV13)

Inactivated Inadequate data for specific recommendation Routine
Polysaccharide

(PPSV23)

Inactivated Inadequate data for specific recommendation Routine This vaccine has been found to be safe in 2nd and 3rd trimesters, though it seems that it's not effective to prevent infant pneumococcal infection.[9]
Poliovirus Inactivated May be used if needed Routine Indicated for high-risk women (travel to endemic area or occupational exposure)
Rabies virus Inactivated May be used if needed Travel and other Post-exposure prophylaxis is indicated.
Smallpox Live Recommended after exposure Travel and other Pre-exposure prophylaxis is not recommended.
TDaP Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis Inactivated Recommended Routine
  • Preferred time: 27-36 weeks, although it can be delivered in any stage of pregnancy
  • If a woman does not receive the vaccine during pregnancy, she should receive it immediately after giving birth.
Typhoid Live and inactivated Inadequate data for specific recommendation Travel and other
  • Live vaccine (Ty21a) is contraindicated
  • Inactivated Vi polysaccharide vaccine should be administered in required clinical setting.
Varicella Live Contraindicated Routine
Yellow fever Live May be used if needed Travel and other If the pregnant women is required to travel to a high-risk endemic area, then it is recommended.
Zoster Live Contraindicated Routine

Influenza vaccine

Administration of the influenza vaccine is now recommended for all pregnant women (during each pregnancy). The vaccine can be administered in any trimester of pregnancy because influenza causes more consequences in pregnant women than those who are not pregnant. Furthermore, infants under 6 months of age are at the greatest risk of complications and death associated with influenza.[10] Influenza infection is associated with an increased risk of subsequent bacterial infection. particularly pneumococcal infection and disease.[11] This potential risk can be leveraged from early infancy by maternal immunization with influenza vaccine.

Pertussis vaccine

The reason for pertussis vaccination in pregnancy is to prevent infants from developing pertussis. TDaP is the prescribed vaccine for this purpose. Current recommendations allow for administration of the pertussis vaccination during any trimester of pregnancy, though with a preference for administration late in a pregnancy: a gestational age of 27 to 36 weeks in the United States and 20 to 32 weeks in the United Kingdom.[12]

Future perspective

Recently, there have been increasing efforts to develop new vaccines for pregnant women. Respiratory syncytial virus (RSV) and group B streptococcus have been areas of great progress recently.

Respiratory Syncytial Virus Vaccine

Due to the high mortality associated with RSV infection in early infancy, it is important to develop a vaccine against it that can prevent this infection in newborns. RSV is the leading cause of viral acute lower respiratory tract illness, and the highest associated morbidity is found among preterm infants.[13] 2 to 3% of all neonatal deaths in the United States can be attributed to RSV.[14] Vaccines in early and preclinical development include live attenuated, whole inactivated, particle-based, subunit, nucleic acid, and gene-based vector vaccines. However, they are still in developing stages and have not been approved for clinical use.

Group B Streptococcal Vaccine

Group B streptococcus is cosidered a potential threat in early infancy. It may cause serious illnesses, especially in preterm infants, including: sepsis, pneumonia, and meningitis.[15] Group B streptococcus may also result in stillbirth. The most important means of transmission is from the birth canal during delivery (i.e., vertical transmission). A maternal group B streptococcal vaccine could help prevent infection in early infancy. Recently, monovalent and trivalent conjugate vaccine candidates have been evaluated in clinical trials awaiting results and approval.[16]

Refernces

  1. ↑ Lindheimer MD, Cunningham FG (2014). "Pregnancy and infection". N. Engl. J. Med. 371 (11): 1076–7. doi:10.1056/NEJMc1408436#SA3. PMID 25207785.
  2. ↑ Straub RH (2007). "The complex role of estrogens in inflammation". Endocr. Rev. 28 (5): 521–74. doi:10.1210/er.2007-0001. PMID 17640948.
  3. ↑ Szekeres-Bartho J, Wegmann TG (1996). "A progesterone-dependent immunomodulatory protein alters the Th1/Th2 balance". J. Reprod. Immunol. 31 (1–2): 81–95. PMID 8887124.
  4. ↑ 4.0 4.1 Robinson DP, Klein SL (2012). "Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis". Horm Behav. 62 (3): 263–71. doi:10.1016/j.yhbeh.2012.02.023. PMC 3376705. PMID 22406114.
  5. ↑ Pazos M, Sperling RS, Moran TM, Kraus TA (2012). "The influence of pregnancy on systemic immunity". Immunol. Res. 54 (1–3): 254–61. doi:10.1007/s12026-012-8303-9. PMID 22447351.
  6. ↑ Schlaudecker EP, McNeal MM, Dodd CN, Ranz JB, Steinhoff MC (2012). "Pregnancy modifies the antibody response to trivalent influenza immunization". J. Infect. Dis. 206 (11): 1670–3. doi:10.1093/infdis/jis592. PMID 22984116.
  7. ↑ Sperling RS, Engel SM, Wallenstein S, Kraus TA, Garrido J, Singh T, Kellerman L, Moran TM (2012). "Immunogenicity of trivalent inactivated influenza vaccination received during pregnancy or postpartum". Obstet Gynecol. 119 (3): 631–9. doi:10.1097/AOG.0b013e318244ed20. PMC 3327739. PMID 22353963.
  8. ↑ Munoz FM, Bond NH, Maccato M, Pinell P, Hammill HA, Swamy GK, Walter EB, Jackson LA, Englund JA, Edwards MS, Healy CM, Petrie CR, Ferreira J, Goll JB, Baker CJ (2014). "Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial". JAMA. 311 (17): 1760–9. doi:10.1001/jama.2014.3633. PMC 4333147. PMID 24794369.
  9. ↑ Chaithongwongwatthana S, Yamasmit W, Limpongsanurak S, Lumbiganon P, Tolosa JE (2015). "Pneumococcal vaccination during pregnancy for preventing infant infection". Cochrane Database Syst Rev. 1: CD004903. doi:10.1002/14651858.CD004903.pub4. PMID 25613573.
  10. ↑ Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, Glover MJ, Likos AM, Posey DL, Klimov A, Lindstrom SE, Balish A, Medina MJ, Wallis TR, Guarner J, Paddock CD, Shieh WJ, Zaki SR, Sejvar JJ, Shay DK, Harper SA, Cox NJ, Fukuda K, Uyeki TM (2005). "Influenza-associated deaths among children in the United States, 2003-2004". N. Engl. J. Med. 353 (24): 2559–67. doi:10.1056/NEJMoa051721. PMID 16354892.
  11. ↑ O'Brien KL, Walters MI, Sellman J, Quinlisk P, Regnery H, Schwartz B, Dowell SF (2000). "Severe pneumococcal pneumonia in previously healthy children: the role of preceding influenza infection". Clin. Infect. Dis. 30 (5): 784–9. doi:10.1086/313772. PMID 10816149.
  12. ↑ "Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women--Advisory Committee on Immunization Practices (ACIP), 2012". MMWR Morb. Mortal. Wkly. Rep. 62 (7): 131–5. 2013. PMID 23425962.
  13. ↑ Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O'Brien KL, Roca A, Wright PF, Bruce N, Chandran A, Theodoratou E, Sutanto A, Sedyaningsih ER, Ngama M, Munywoki PK, Kartasasmita C, Simões EA, Rudan I, Weber MW, Campbell H (2010). "Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis". Lancet. 375 (9725): 1545–55. doi:10.1016/S0140-6736(10)60206-1. PMC 2864404. PMID 20399493.
  14. ↑ Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA (2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. PMID 23245604.
  15. ↑ Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH, Petit S, Craig AS, Schaffner W, Zansky SM, Gershman K, Stefonek KR, Albanese BA, Zell ER, Schuchat A, Schrag SJ (2008). "Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005". JAMA. 299 (17): 2056–65. doi:10.1001/jama.299.17.2056. PMID 18460666.
  16. ↑ Madhi SA, Cutland CL, Jose L, Koen A, Govender N, Wittke F, Olugbosi M, Meulen AS, Baker S, Dull PM, Narasimhan V, Slobod K (2016). "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. 16 (8): 923–34. doi:10.1016/S1473-3099(16)00152-3. PMID 27139805.
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