Immunization during pregnancy

Newborns are at increased risk of infection, particularly before they receive their first infant vaccinations. For this reason, certain vaccinations are offered during pregnancy in order to induce an antibody response, resulting in the passage of antibody across the placenta and into the fetus: this confers passive immunity on the newborn. As early as 1879, it was noted that infants born following smallpox vaccination in pregnancy were themselves protected against smallpox.[7] However, the original smallpox vaccination was never widely used during pregnancy because, as a live vaccine, its use is contraindicated.

Tetanus is a bacterial infection caused by Clostridium tetani. Newborns can be infected via their unhealed umbilical stump, particularly when the umbilical cord is cut with a non-sterile instrument, and suffer a generalised infection. The tetanus toxoid vaccine was first licensed for use in 1938 and, during the 1960s, it was noted that tetanus vaccination in pregnancy could prevent neonatal tetanus.[8] Subsequent trials showed that vaccination of pregnant women reduces infant deaths from tetanus by 94%.[9][10] In 1988, the World Health Assembly passed a resolution to use maternal vaccination to eliminate neonatal tetanus by the year 2000. Although neonatal tetanus has not yet been eliminated, by 2017 there were an estimated 31,000 annual infant deaths from tetanus, down from 787,000 in 1987.[11]

Whooping cough, or pertussis, is a contagious respiratory disease caused by the bacteria Bordetella pertussis. It is fatal in an estimated 0.5% of infants in the USA.[12] The first vaccine against whooping cough was developed in the 1930s, and in the 1940s a study found that vaccination in pregnancy protected infants against developing whooping cough.[13]

The tetanus and whooping cough vaccinations are generally administered in combination during pregnancy, for example as the DTaP vaccine (which also protects against diphtheria) or the 4-in-1 vaccine (which also protects against diphtheria and polio).

Influenza is a respiratory infection caused by influenza viruses. Pregnant women are disproportionately affected by influenza: in the 1918 pandemic, mortality rates as high as 27% were reported in this population and in the 1957 pandemic, nearly 20% of deaths in pregnancy were attributed to influenza. In the 2009 pandemic, even with medical advances, pregnant women accounted for a disproportionately high percentage of deaths.[14]

The influenza vaccine was first used in the US military from 1938, and then in the civilian population from the 1940s. Given the increased risk of influenza during pregnancy, public health bodies in the USA recommended that pregnant women should be prioritised for influenza vaccination from the 1960s,[15] with the CDC endorsing the recommendation from 1997.[16] However, it was not until 2005 that a randomised clinical trial formally demonstrated the efficacy of influenza vaccination in pregnancy.[17]

Following the 2009 pandemic, both Australia and the UK added influenza vaccination to the recommended schedule for pregnant women.

COVID-19 is a respiratory infection caused by the SARS-CoV2 virus. Before COVID-19 vaccines were available, pregnant women who caught the disease were at increased risk of needing intensive care, invasive ventilation or ECMO, but not at increased risk of death.[18] Infection significantly increased the risk of preterm birth, stillbirth and pre-eclampsia.[19]

mRNA COVID-19 vaccines were first rolled out in December 2020. At this time, in recognition of the risks posed by COVID-19 disease in pregnancy, the US and Israel offered the vaccines to all pregnant women shortly afterwards, and the first safety and effectiveness data therefore came from these vaccines and these nations.[20] By March 2022, formal studies on the safety of COVID-19 vaccination in pregnancy including more than 185,000 individuals had found no increased risk of any obstetric complications following COVID-19 vaccination [20] and in April 2022, a systematic review and meta-analysis of the data showed that, during the pandemic, COVID-19 vaccination reduced the risk of stillbirth by approximately 15%.[21] At this time, 110 countries recommended COVID-19 vaccination in pregnancy, with a further 72 offering (but not recommending) vaccination.[22]

Rubella, or German measles, is an infection caused by the rubella virus. In childhood, it usually causes a mild disease but infection in pregnancy can result in fetal infection, or congenital rubella syndrome, which causes neonatal deaths, deafness, blindness and intellectual disabilities. The first rubella vaccine was licensed for use in 1969, with its development largely spurred by the heavy burden of congenital rubella experienced in the 1960s.[23]

Because the rubella vaccine is a live attenuated vaccine, there is a theoretical risk that it could cause fetal infection, although this has never been seen to occur. Therefore, rubella vaccination is usually avoided during pregnancy. Rather, vaccination is offered to children to reduce the prevalence of rubella virus in circulation and/or to adolescent girls, to boost their immunity before they are likely to conceive.[24][25]