Optimising the Timing of whooping cough Immunisation in MUMs: a randomised controlled trial investigating the timing of pertussis vaccination in pregnancy (OpTIMUM): a protocol paper

Abstract

Background: Pertussis is a highly infectious respiratory illness caused by the bacteria Bordetella pertussis. A resurgence of pertussis, even in countries with good vaccine coverage, has led to an increase in infant deaths. In response to this, many countries have introduced pertussis vaccination in pregnancy. This strategy is effective at preventing infant disease, but there remains uncertainty about what gestational timing is best to ensure maximal protection of the infant. These uncertainties are the rationale for this randomised controlled trial and a sub-study investigating pertussis-specific antibody in breastmilk. Protocol: We will recruit 354 pregnant women and will randomise them to receive their pertussis vaccination in one of three gestational age windows: ≤23+6, 24-27+6 and 28-31+6 weeks of gestation. Vaccination will be with Boostrix-IPV® and participants will be asked to complete a symptom diary for seven days following vaccination. Blood sampling will be performed prior to vaccination, two weeks following vaccination and at the time of delivery. A cord blood sample will be collected at delivery and a blood sample collected from the infant 4-10 weeks after completion of the primary immunisations. Individuals participating in the breastmilk sub-study will provide a sample of colostrum within 48 hours of delivery and samples of breastmilk at two weeks and around five-six months. Blood samples will be analysed using enzyme linked immunosorbent assay (ELISA) techniques for pertussis toxin, filamentous haemagglutinin and pertactin. A subset of serum samples will also be analysed using a functional assay. Colostrum and breastmilk samples will be analysed using functional assays. Discussion: Although pertussis vaccination has been shown to be safe and effective in pregnancy there remains debate about the optimal timing for the administration during pregnancy. This study will investigate antibody responses in serum and breastmilk when vaccination is performed in three different time periods. Clinicaltrials.gov registration: NCT03908164 (09/04/2019)

The current state of pertussis vaccination in pregnancy around the world, with recommendations for improved care: Consensus statements from the Global Pertussis Initiative

“…37 A recent study showed that vaccine administered between 16 and 32 weeks of pregnancy provided similar levels of antipertussis toxin and antipertactin IgG concentrations. 38 However, antifilamentous hemagglutinin IgG concentrations were shown to be increased with advanced gestational age at the time of vaccination in pregnancy that is between 28 and 32 gestational weeks. 38 Another factor in optimizing vaccine effectiveness is prematurity.…”

“…38 However, antifilamentous hemagglutinin IgG concentrations were shown to be increased with advanced gestational age at the time of vaccination in pregnancy that is between 28 and 32 gestational weeks. 38 Another factor in optimizing vaccine effectiveness is prematurity. An independent risk factor for severe morbidity and mortality related to pertussis infection is indeed preterm birth.…”

“…6,7,[44][45][46][47][48][49][50] Studies are currently underway comparing the response to the Tdap vaccine before 24 weeks, between 24 and 28 weeks, and between 28 and 31 weeks, with initial results showing high placental pertussis antibody transfer to the fetus and that persisted well after birth. 38 There is no question that pertussis vaccination in pregnancy provides significant protection to the newborn and infant (when compared with children born to unvaccinated individuals). However, the optimal timing of vaccination remains an area of great debate, and timing is likely to be linked to additional factors related to the pregnant person and the developing fetus(es).…”

Update on Vaccines in Antenatal Care

“…A recent study reported equivalent concentrations of IgG antibodies in infants born to mothers who received the pertussis vaccine at 3 different time intervals in pregnancy, supporting a broader interval of 16–32 weeks. 1 Safety evaluations of the Tdap vaccine have not revealed any significant concerns associated with its use during pregnancy. Maternal vaccination with a pertussis-containing vaccine leads to elevated antibody levels in newborns, which persist for at least 2–3 months.…”

Optimising the timing of whooping cough immunisation in mums (OpTIMUM) through investigating pertussis vaccination in pregnancy: an open-label, equivalence, randomised controlled trial

“…11 Finally, an observational study from Switzerland in 2016 showed that anti-pertussis toxin and anti-filamentous haemagglutinin concentrations were higher in cord blood following vaccination in the second trimester than following vaccination in the third trimester. 12 Following this report, and mindful of the logistical benefits of offering vaccination in a wider time window, the UK extended the recommended window for vaccination to [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] weeks in 2016.…”