Maternal immunization

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 to reduce childhood mortality and morbidity. Vaccination schedule starts at early infancy and it's not complete by age of 6 months. Therefore, most of the children do not have coverage during the early infancy with adequate protection 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 became to consideration to cover this gap. However it can protect mother from acquiring infection it is also effective for infant protection.

Immunology

Maternal immunity changes during the pregnancy under influence of hormonal changes. Increased level of estrogen and progesterone are the most important factors for these changes. Increased level of estradiol is associated with increased level of T-helper type 2 cell response compared to type 1 T-cells. However, increased level of progesterone may result in decrease in immune response and alteration in immune system. Other aspect of immune response such as, phagocytosis and number of neutrophils and monocytes remains unchanged.
These changes (alteration in cell mediated immunity) explain sub-optimal immune response to some certain viral infections such as influenza. Furthermore, it justifies the need for immunization against these infections. Other parts of immune system remains intact during pregnancy and immunosuppresion does not encounter during pregnancy.
Clinical effectiveness of vaccination during pregnancy is maintained and changes in immune balance does not influence their effectiveness.

Maternal immunization recommendation

Inactivated influenza and combined tetanus-diphteria-acellular pertussis (TDaP) are recommended for pregnant women in the U.S. Hepatitis B and hepatitis E vaccines are recommended in some other countries.
The following table summarize the 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 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 report for BCG adverse effects in pregnancy
HAV		Inactivated	Recommended for specific indications	Routine	Indications: History of injection or noninjection illicit drug use Work with HAV-infected primates Work with HAV in a research laboratory Chronic liver disease Receive 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: If have had a HBsAg-positive sex partner Have had more than one sex partner during the previous 6 mo Have been evaluated or treated for an STD History of recent or current injection-drug use The recommended schedule is 0, 1, and 6 mo.
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 a high risk area.
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	It found to be safe in 2nd and 3rd trimesters. But, it seems that it's not effective to prevent infant pneumococcal infection.(19)
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

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 non pregnant. furthermore, infants under 6 months of age are at greatest risk of complications and death associated with influenza.(33) Influenza infection is associated with an increased risk of subsequent bacterial infection particularly, pneumococcal infection and disease.(41) This potential risk can be leveraged from early infancy by maternal immunization with influenza vaccine.

Pertussis vaccine

The reason of pertussis vaccination in pregnancy, is to prevent infants from pertussis. TDaP is prescribed vaccine for this purpose. Current recommendationsallow for pertussis vaccination in any trimester of pregnancy but with a preference for late pregnancy: a gestational age of 27 to 36 weeks in the United States and 20 to 32 weeks in the United Kingdom.(45-47)

Future perspective

There has been increasing effort to develop new vaccines for pregnant women. Respiratory syncytial virus (RSV) and group B streptococcus have the most progress recently.

Respiratory Syncytial Virus Vaccine

Due to high mortality of RSV infection in early infancy, it is important to develop vaccine against it to prevent this infection in newborns. RSV is the leading cause of viral acute lower respiratory tract illness, and the highest morbidity is among preterm infants.57,58 2 to 3% of all neonatal deaths in the United States is attributed to RSV.58 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. 60

Group B Streptococcal Vaccine

Group B streptococcus is cosidered as potential threat in early infancy. It may cause serious illnesses especially in preterm infants including: sepsis, pneumonia and meningitis.67,68 Also, it may cause stillbirth. The most important way of transmission is from the birth canal during delivery. A maternal group B streptococcal vaccine could help preventing infection in early infancy. Recently, monovalent and trivalent conjugate vaccine candidates have been evaluated in clinical trials awaiting the results and approval.71-7