Women's views and experiences of accessing pertussis vaccination in pregnancy and infant vaccinations during the COVID-19 pandemic: A multi-methods study in the UK.

BACKGROUND: COVID-19 changed access to healthcare, including vaccinations, in the United Kingdom (UK). This study explored UK women's experiences of accessing pertussis vaccination during pregnancy and infant vaccinations during COVID-19. METHODS: An online cross-sectional survey was completed, between 3rd August-11th October 2020, by 1404 women aged 16+ years who were pregnant at some point after the first UK lockdown from March 23rd, 2020. Ten follow-up semi-structured interviews were conducted. RESULTS: Most women surveyed were pregnant (65.7%) and a third postnatal (34.3%). Almost all women (95.6%) were aware that pertussis vaccination is recommended in pregnancy. Most pregnant (72.1%) and postnatal women (84.0%) had received pertussis vaccination; however, access issues were reported. Over a third (39.6%) of women had a pregnancy vaccination appointment changed. COVID-19 made it physically difficult to access pregnancy vaccinations for one fifth (21.5%) of women and physically difficult to access infant vaccinations for almost half of women (45.8%). Nearly half of women (45.2%) reported feeling less safe attending pregnancy vaccinations and over three quarters (76.3%) less safe attending infant vaccinations due to COVID-19. The majority (94.2%) felt it was important to get their baby vaccinated during COVID-19. Pregnant women from ethnic-minorities and lower-income households were less likely to have been vaccinated. Minority-ethnicity women were more likely to report access problems and feeling less safe attending vaccinations for both themselves and their babies. Qualitative analysis found women experienced difficulties accessing antenatal care and relied on knowledge from previous pregnancies to access vaccines in pregnancy. CONCLUSION: During the ongoing and future pandemics, healthcare services should prioritise equitable access to routine vaccinations, including tailoring services for ethnic-minority families who experience greater barriers to vaccination.

Women's views on accepting COVID-19 vaccination during and after pregnancy, and for their babies: a multi-methods study in the UK.

BACKGROUND: COVID-19 vaccines are advised for pregnant women in the United Kingdom (UK) however COVID-19 vaccine uptake among pregnant women is inadequate. METHODS: An online survey and semi-structured interviews were used to investigate pregnant women's views on COVID-19 vaccine acceptability for themselves when pregnant, not pregnant and for their babies. One thousand one hundred eighty-one women, aged over 16 years, who had been pregnant since 23rd March 2020, were surveyed between 3rd August-11th October 2020. Ten women were interviewed. RESULTS: The majority of women surveyed (81.2%) reported that they would 'definitely' or were 'leaning towards' accepting a COVID-19 vaccine when not pregnant. COVID-19 vaccine acceptance was significantly lower during pregnancy (62.1%, p < 0.005) and for their babies (69.9%, p < 0.005). Ethnic minority women were twice as likely to reject a COVID-19 vaccine for themselves when not pregnant, pregnant and for their babies compared to women from White ethnic groups (p < 0.005). Women from lower-income households, aged under 25-years, and from some geographic regions were more likely to reject a COVID-19 vaccine when not pregnant, pregnant and for their babies. Multivariate analysis revealed that income and ethnicity were the main drivers of the observed age and regional differences. Women unvaccinated against pertussis in pregnancy were over four times more likely to reject COVID-19 vaccines when not pregnant, pregnant and for their babies. Thematic analysis of the survey freetext responses and interviews found safety concerns about COVID-19 vaccines were common though wider mistrust in vaccines was also expressed. Trust in vaccines and the health system were also reasons women gave for accepting COVID-19 vaccines. CONCLUSION: Safety information on COVID-19 vaccines must be clearly communicated to pregnant women to provide reassurance and facilitate informed pregnancy vaccine decisions. Targeted interventions to promote COVID-19 vaccine uptake among ethnic minority and lower-income women may be needed.

Modification of innate immune responses to Bordetella pertussis in babies from pertussis vaccinated pregnancies.

BACKGROUND: Tetanus, diphtheria, acellular pertussis, inactivated polio (Tdap-IPV) vaccines administered during pregnancy protect young infants from Bordetella pertussis (B. pertussis) infection. Whilst the impact of maternal Tdap-IPV vaccination on infants' humoral response to subsequent pertussis immunisation has been investigated, little is known about any impact on innate responses. METHODS: We investigated the immune response to B. pertussis in mothers and infants from Tdap-IPV-vaccinated and unvaccinated pregnancies, utilising a whole blood assay and flow cytometric phenotyping of neonatal natural killer (NK) cells, monocytes and dendritic cells. Blood was collected from mother and umbilical cord at birth, and from infants at seven weeks (one week pre-primary pertussis immunisation) and five months of age (one month post-primary pertussis immunisation). 21 mothers and 67 infants were studied. FINDINGS: Vaccinated women had elevated pro-inflammatory cytokine responses to B. pertussis. At birth, babies of vaccinated women had elevated IL-2 and IL-12 responses, elevated classical monocyte proportions, and reduced monocyte and NK cell cytokine responses. The elevated IL-2 response persisted to seven weeks-of-age, when lower IL-10 and IL-13 responses were also seen. One-month post-primary pertussis vaccination, infants from vaccinated pregnancies still had lower IL-10 responses to B. pertussis, as well as lower IL-4. INTERPRETATION: This study suggests that pertussis vaccination during pregnancy impacts infant cellular immune responses, potentially contributing to the modification of antibody responses already reported following primary immunisation against B. pertussis. FUNDING: National Institute for Health Research Imperial Biomedical Research Centre and IMmunising PRegnant women and INfants neTwork (funded by the GCRF Networks in Vaccines R&D).

Evaluation of a midwife-led, hospital based vaccination service for pregnant women.

Background: Vaccines against whooping cough (pertussis) and seasonal-influenza are recommended for pregnant women in England. Uptake however varies regionally and by ethnicity. Pregnant women are traditionally vaccinated in primary care, though some hospitals now offer vaccines through antenatal clinics. This mixed-methods evaluation describes the demographic characteristics of women seen in a hospital midwife-led antenatal vaccine clinic and explores vaccine decision making. Methods: Descriptive statistics of women seen in a London hospital's midwife-led vaccine clinic were generated from electronic routine maternity records, including data on ethnicity, parity, age and deprivation indices. Reasons for vaccine decline given by women to midwives were categorized by themes. Qualitative interviews of women seen in the clinic were also undertaken. Results: Between 1st April 2017 and 31st March 2018 the vaccine clinic saw 1501 pregnant women. Of these, 83% received pertussis vaccine and (during flu season) 51% received influenza vaccine, from the clinic. Fewer Black Afro-Caribbean women seen by the clinic were vaccinated, compared to other ethnicities with only 68% receiving pertussis and 34% flu vaccines respectively (p < .05). Among all women delivering at the hospital over the year, 42%, (1334/3147) were vaccinated by the clinic. Qualitative interviews found that reassurance from healthcare professionals, particularly midwives, was the most important factor influencing maternal vaccine decisions. Conclusions: Midwife-led hospital clinics can offer an effective alternative to primary care provision for vaccines in pregnancy. Consistent with previous work, vaccine uptake varied by ethnicity. Midwives play a key role in the provision of vaccine services and influence women's vaccine decisions.

Update on Transplacental Transfer of IgG Subclasses: Impact of Maternal and Fetal Factors.

Transplacental antibody transfer from mother to fetus provides protection from infection in the first weeks of life, and the four different subclasses of IgG (IgG1, IgG2, IgG3, and IgG4) have diverse roles in protection against infection. In this study, we evaluated concentrations and transplacental transfer ratios of the IgG subclasses in a healthy UK-based cohort of mother-cord pairs, and investigated associations with maternal, obstetric, and fetal factors. In agreement with previous studies, we found a strong association between maternal and cord IgG for all subclasses. We report a transfer efficiency hierarchy of IgG1>IgG3>IgG4=IgG2 in our study population, and our review of the literature demonstrates that there is no consensus in the hierarchy of subclass transfer, despite the commonly made statement that the order is IgG1>IgG4>IgG3>IgG2. We report additional data regarding negative associations between elevated maternal IgG concentrations and maternal/cord transfer ratios, finding an effect on IgG1, IgG2, and IgG3 subclasses. Levels of IgG subclasses were the same between venous and arterial blood samples from the umbilical cord, but there was a significantly higher level of total IgG in arterial blood. We found no correlation between placental FcRn protein levels and IgG transfer in our cohort, suggesting that IgG is the main determinant of observed differences in transplacental transfer ratios at term. Neonatal IgG1 and IgG4 levels were increased with later gestation at delivery, independent of any increase in transplacental transfer, indicating that the benefit of later gestation is through accumulation of these subclasses in the fetus. Neonatal IgG2 levels and transfer ratios were reduced in rhesus-negative pregnancies, suggesting that administered anti-D antibodies may compete for transplacental transfer of this subclass. Maternal influenza vaccination resulted in elevated maternal and neonatal levels of IgG4, whereas maternal Tdap vaccination had no impact on neonatal levels of the subclasses, nor transfer. However, within Tdap vaccinated pregnancies, later gestation at Tdap vaccination was associated with higher transplacental transfer. Our study provides information regarding levels and transfer of IgG subclasses in healthy term pregnancies and demonstrates the importance of recording detailed clinical information in studies of antibody transfer, including parity, ethnicity, and timing of maternal vaccine delivery.

The relationship between concentration of specific antibody at birth and subsequent response to primary immunization.

BACKGROUND AND AIMS: Trans-placentally acquired antibodies can protect infants from infection in the first months of life. However, high concentrations of antibody at birth may impact the infant's own immune response to primary immunization. We examine the relationship between concentration of specific antibody to Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid and pneumococcal antigens at birth and following primary immunization. METHODS: Healthy mother-infant pairs were recruited from a UK maternity unit. Peripheral blood samples were obtained at birth and 4 weeks after primary immunization. Specific antibody concentrations were determined using enzyme-linked immunosorbent assays. Pertussis antibody concentrations >50 IU/ml, Tetanus antibody levels >0.1 IU/ml and Hib antibody levels >0.15 mg/l were regarded as protective. RESULTS: Following primary immunization, 35/36 (97%) infants had specific antibody concentrations associated with protection against Hib, 32/36 (89%) against pertussis and 36/36 (100%) against tetanus. Concentrations of all specific antibodies were significantly higher than at birth (p<0.0001), except anti-tetanus toxoid, p=0.41. However, there was an inverse correlation between infant antibody concentration at birth and fold-increase in antibody concentration post-immunization for tetanus: rs -0.86 (95%CI -0.93 to -0.74), p<0.0001; pneumococcus: rs -0.82 (95% CI -0.91 to -0.67), p<0.0001; pertussis: rs -0.77 (95% CI -0.89 to -0.58), p<0.0001 and Hib: rs -0.66 (95%CI -0.82 to -0.42), p<0.0001. The highest concentrations of specific IgG at birth were associated with lower concentrations post-immunization for tetanus (p=0.009) and pneumococcus (p=0.03). This association was not observed for Hib (p=0.88) or pertussis (p=0.14). CONCLUSION: Higher antibody concentration at birth appeared to inhibit the response to infant immunization for tetanus and pneumococcus; the effect was less marked for Hib and pertussis. However, the majority of infants achieved high antibody levels post-immunization. This supports maternal immunization, as high levels of maternally derived antibody at birth may not inhibit infants' immunization responses in a clinically relevant manner.

Specific antibodies against vaccine-preventable infections: a mother-infant cohort study.

OBJECTIVES: To determine maternal and neonatal specific antibody levels to selected vaccine-preventable infections (pertussis, Haemophilus influenzae type b (Hib), tetanus and pneumococcus). DESIGN: Prospective cohort study. SETTING: A UK secondary care maternity unit (March 2011-January 2012). PARTICIPANTS: Mothers and infants within 72 h of delivery were eligible. Unwell individuals, mothers less than 18 years of age, and infants born at less than 36 weeks gestation, or weighing less than 2500 g, were excluded. HIV-infected mothers were included. 112 mother-infant pairs were recruited. Samples from 111 mothers and 109 infants (108 pairs) were available for analysis. OUTCOME MEASURES: Specific antibody levels were determined using standard commercial ELISAs. Specific antibody to pertussis antigens (PT and FHA) of >50 IU/ml, defined as 'positive' by the test manufacturer, were interpreted as protective. Antitetanus antibody titres >0.1 IU/ml and anti-Hib antibody titres >1 mg/l were regarded as protective. RESULTS: Only 17% (19/111) of women exhibited a protective antibody response against pertussis. 50% (56/111) of women had levels of antibody protective against Hib and 79% (88/111) against tetanus. There was a strong positive correlation between maternal-specific and infant-specific antibodies' responses against pertussis (rs=0.71, p<0.001), Hib (rs=0.80, p<0.001), tetanus (rs=0.90, p<0.001) and pneumococcal capsular polysaccharide (rs=0.85, p<0.001). Only 30% (33/109) and 42% (46/109) of infants showed a protective antibody response to pertussis and Hib, respectively. Placental transfer (infant:mother ratio) of specific IgG to pertussis, Hib, pneumococcus and tetanus was significantly reduced from HIV-infected mothers to their HIV-exposed, uninfected infants (n=12 pairs) compared with HIV-uninfected mothers with HIV-unexposed infants (n=96 pairs) by 58% (<0.001), 61% (<0.001), 28% (p=0.034) and 32% (p=0.035), respectively. CONCLUSIONS: Low baseline antibody levels against pertussis in this cohort suggest the recently implemented UK maternal pertussis immunisation programme has potential to be effective.