Whooping cough (pertussis) and influenza vaccination for pregnant women

Safety of pertussis vaccination in pregnant women in UK: observational study

• Analysis of 20,074 pregnant women vaccinated in the UK during the first 6 months of their pertussis vaccination campaign.
• Uptake of vaccination program approx. 60%.
• Study found no evidence of an increased risk of adverse events related to pregnancy, in particular, no evidence of an increased risk of stillbirth.
• There was no increased risk of maternal or neonatal death, (pre-) eclampsia, haemorrhage, foetal distress, uterine rupture, placenta or vasa praevia, caesarean delivery, low birth weight, or child renal failure.
• These initial data provide evidence for health professionals and the public to balance against the benefits of the vaccine and can help to inform international vaccination policy making.

Amirthalingam G, Andrews N, Campbell H, Riberio S, Kara E, Donegan K, Fry NK, Miller E, Ramsay M. Lancet, published online 16 July 2014

Effectiveness of maternal pertussis vaccination in England: an observational study

• Assessment of maternal vaccination program in England shows a high point estimate for vaccine effectiveness of 91% and suggests that the protection was mainly due to placental transfer of antibodies and reduced maternal exposure.
• Vaccine effectiveness was 90% when the analysis was restricted to children younger than 2 months.

Association of Tdap Vaccination with acute events and adverse birth outcomes among pregnant women with prior tetanus-containing immunizations

• A retrospective cohort study in 29,155 pregnant women from 2007 – 2013 using data from 7 vaccine Safety Datalink sites in California, Colorado, Minnesota, Oregon, Washington and Wisconsin
• Study sought to determine whether women receiving Tdap vaccine during pregnancy given in close intervals from prior tetanus containing vaccinations, is associated with acute adverse events in mothers and adverse birth outcomes in neonates.
• Among women who received Tdap vaccination during pregnancy, there was no increased risk of acute adverse events or adverse birth outcomes for those who had been previously vaccinated less than 2 years before or 2 to 5 years before compared with those who had been vaccinated more than 5 years before.
• Findings suggest that relatively recent receipt of a prior tetanus-containing vaccination does not increase risk after Tdap vaccination in pregnancy.

Dabrera G, Amirthalingam G, Andrews N, Campbell H, Ribeiro S , Kara E, Fry NK, Ramsay M. Clin Infect Dis. 2015 Feb 1;60(3):333-7.

A case-control study to estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and Wales, 2012-2013.

• The objective of this study was to estimate the effectiveness of maternal pertussis vaccination in protecting infants against laboratory-confirmed pertussis infection.
• This research was a case-control study undertaken in England and Wales between October 2012 and July 2013. Cases where infants aged <8 weeks at onset with pertussis infection tested by real-time polymerase chain reaction or culture.
• Family doctors of each case were asked to identify healthy infants born consecutively after the case in each practice, to act as controls. Fifty-eight cases and 55 controls were included in this study. Odds ratios (ORs) were calculated for the association between maternal vaccination and infant pertussis infection. The vaccine effectiveness (VE) was calculated as 1 - OR. This was adjusted for sex, geographical region, and birth period.

Munoz FM, Bond NH, Maccato M, et al.. JAMA 2014;311:1760-9.

Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunisation during pregnancy in mothers and infants: a randomized clinical trial

• The study sought to evaluate the safety and immunogenicity of Tdap immunisation during pregnancy and its effect on infant responses to diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine.
• This was a clinical trial conducted from 2008 to 2012. Forty-eight pregnant women aged 18 to 45 years received Tdap (n = 33) or placebo (n = 15) at 30 to 32 weeks’ gestation, with crossover immunisation postpartum.
• This preliminary assessment did not find an increased risk of adverse events among women who received Tdap vaccine during pregnancy or their infants. For secondary outcomes, maternal immunisation with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap immunisation during pregnancy.

Top G and Paeps A Flemish Agency for Care and Health, Poster presentation

Pertussis vaccination and epidemiology in Flanders: the need for future alternative vaccination strategies

• Following the Belgian Superior Health Council (National Immunisation Technical Advisory Group-NITAG) recommendation that all pregnant women between 24–32 weeks gestation receive pertussis vaccination, the city of Flanders will add pertussis vaccination of pregnant women in each pregnancy to their vaccination program from 1 July 2014.

Zheteyeva YA, Moro PL et. al.
American Journal of Obstetrics and Gynaecology 2012; 207: 59. e1-7.

Adverse event reports after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines in pregnant women

• Analysis of 132 adverse event reports to the Vaccine Adverse Event Reporting System (VAERS) from pregnant women who received acellular pertussis vaccine.
• In a time when pertussis vaccination was not routinely recommended for pregnant women, the study found no concerning patterns in maternal, infant or foetal outcomes.

American College of Obstetricians and GynaecologistsObstetrics and Gynaecology 2013; 121: 1411-4.

Update on immunisation and pregnancy: tetanus, diphtheria and pertussis vaccination.  Committee Opinion No. 566.

• Overview of the Centres for Disease Control and Preventions Advisory Committee on Immunisation Practices recommendation a dose of Tdap for pregnant women during each pregnancy, irrespective of prior Tdap vaccination history.
• The American College of Obstetricians and Gynaecologists support the revised recommendations.

World Health Organisation (WHO)
WHO, 14 March 2014

WHO Strategic Advisory Group of Experts (SAGE) pertussis working group: background paper, SAGE April 2014

• Summarises key conclusions based on data from 15 high income and 4 middle income countries (where relevant):
  • UK experience indicates a high impact of vaccination with an overall reduction in infant mortality.
  • Vaccine is safe and effective to use in pregnant women (acellular pertussis).
  • Some evidence of reduced response to pertussis antigens in infants of vaccinated women (to date there is no evidence of increased risk of pertussis in infants aged 3–11 months).
  • “Vaccination of pregnant women is considered likely to be the most cost-effective complementary strategy to prevent pertussis associated infant mortality, more effective than cocooning”.

Pregnancy outcomes after antepartum Tetanus, Diphtheria and acellular pertussis vaccinations.

• This study evaluated pregnancy outcomes of 7,152 women who received tetanus, diphtheria, and acellular pertussis (Tdap) vaccination at or after 32 weeks of gestation. Outcomes from consecutive pregnancies during which the mother received Tdap were also analyzed.
• No adverse pregnancy outcomes were identified in association with antepartum Tdap vaccination. This remained true in women receiving more than one Tdap vaccine in a 5-year timeframe. This may be the result of a type II error.

Centres for Disease Control
Morbidity and Mortality Weekly Report, 21 October 2011, Vol. 60, No. 41.

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 Immunisation Practices (ACIP), 2011

• Since June 2011, ACIP has recommended use of Tdap in unvaccinated pregnant women in the third trimester.
• ACIP reviewed pregnancy registry data from Vaccine Adverse Event Reporting System (VAERS), Sanofi Pasteur and GlaxoSmithKline (manufacturers of Tdap vaccine).

Centres for Disease Control. MMWR. 2013;62(07):131–135.

Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis (Tdap) Vaccine in Pregnant Women -- Advisory Committee on Immunization Practices (ACIP), 2012

• In October 2011, in an effort to reduce the burden of pertussis in infants, the Advisory Committee on Immunization Practices (ACIP) recommended that unvaccinated pregnant women receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap).
• New data indicate that maternal antipertussis antibodies are short-lived; therefore, Tdap vaccination in one pregnancy will not provide high levels of antibodies to protect newborns during subsequent pregnancies.
• ACIP concluded that experience with tetanus-toxoid containing vaccines suggests no excess risk for severe adverse events for women receiving Tdap with every pregnancy.
• Tdap may be administered any time during pregnancy, but vaccination during the third trimester would provide the highest concentration of maternal antibodies to be transferred closer to birth.
• ACIP recommends that providers of prenatal care implement a Tdap immunisation program for all pregnant women.
• Health-care personnel should administer a dose of Tdap during each pregnancy, irrespective of the patient's prior history of receiving Tdap.

New Zealand Ministry of Health, (NZMoH),Immunisation Handbook 2014, 2^nd edition, April 2016

New Zealand Ministry of Health: Immunisation Handbook 2014

• The NZ MoH website states 'The whooping cough vaccine is safe for use in pregnancy'.
• The NZ MoH states vaccination with Tdap should be offered in every pregnancy (currently funded between 28 and 38 weeks gestation to protect the mother).

Immunisation in Pregnancy and Breastfeeding

• There is no theoretical reason to suspect that adverse events will occur in the fetus or infant following maternal vaccination with inactivated vaccines during pregnancy.
• There are no published data indicating that currently authorized inactivated vaccines are teratogenic or embryotoxic, or have resulted in specific adverse pregnancy outcomes.
• Immunisation with Tdap to date has been shown to be safe in pregnant women and allows high levels of antibody to be transferred to newborns during the first two months of life when the morbidity and mortality from pertussis infection is the highest.
• All pregnant women at 26 weeks of pregnancy or later who have not received a dose of pertussis-containing vaccine in adulthood, should be encouraged to receive Tdap vaccination. Immunisation should not be delayed until close to delivery since this may provide insufficient time for optimal transfer of antibodies and direct protection of the infant against pertussis.

Vaccination of women who are planning pregnancy, pregnant or breastfeeding, and preterm infants

• Studies have found no evidence of an increased risk of adverse pregnancy outcomes related to pertussis vaccination during pregnancy.
• Pertussis vaccination during the third trimester of pregnancy has been shown to be more effective in reducing the risk of infant pertussis than maternal vaccination post partum.

Vaccine Knowledge Project
University of Oxford, England United Kingdom