Pertussis Vaccination in Every Pregnancy: Safe and Effective
I’m now 37 weeks pregnant, and it blows my mind how quickly this pregnancy has flown by. Now the days are ticking by faster than I can tick things off of my to-do list, and I can feel my body warming up for birth with increasing Braxton Hicks contractions and the baby dropping into my pelvis.
Preparing for a new baby means lots of things to me. There is the physical preparation of washing and folding tiny clothes and setting up baby’s space for changing and sleeping (in our bedroom for now). There is the arduous task of coming up with names – two of them, since we don’t know the baby’s sex. There is the mental preparation of imagining life with a new baby, trying to map out a few strategies for coping with wakeful nights and baby-filled days. There are the talks with Cee about how things will change and how they will stay the same, how she can help us with the baby, and how we’ll help her to adapt to the change in her life.
There’s also the very important aspect of making sure that we do everything we can to protect our new baby’s health, especially before the first round of immunizations at 2 months. This baby will be born during the season of flu and cold viruses, and this year is predicted to be a pretty bad one for the flu. Just south of our home in Oregon, California has so far recorded nearly 10,000 cases of pertussis, also known as whooping cough, this year, more than they’ve seen in 70 years. Cee will be exposed to a range of pathogens in preschool, and my husband will encounter them in his job in healthcare. We’ll do our best to protect our baby by leaving our shoes at the front door, changing clothes when needed, and washing our hands frequently. I also plan to breastfeed, which should confer some passive protection to the baby. However, some of the most important protection has hopefully already been given to this baby during pregnancy, because I’ve been vaccinated for both the flu (as soon as the vaccine was available this season, around 26 weeks) and pertussis around 34 weeks.
The flu vaccine was first recommended for pregnant women in 1964,1 and there is a large body of research showing that the flu shot is safe in pregnancy and an effective way of preventing flu infections in expecting moms, which can pose a significant risk to the fetus. There’s also good evidence that influenza antibodies are transferred to the baby in utero,2 reducing baby’s chances of infection and hospitalization with the flu in early infancy.3,4 (Several of the above links direct you to evidence-based articles written by Tara Haelle on her blogs at Red Wine and Apple Sauce and Forbes. If you want to keep up with vaccine and other health news, Tara is an excellent blogger and science journalist to follow.)
The latest news on this year’s flu season is showing that most of the cases seen so far have been identified as being caused by seasonal influenza A H3N2, a nasty strain, and about half of these are a new subtype that isn’t well-covered by this year’s flu vaccine. If you haven’t yet gotten a flu shot this season, don’t let this news deter you. The flu vaccine will still protect you from the older strains of the flu and might decrease the severity of an infection with the newer type. The vaccine is very safe and still offers the best protection against the flu for you and your baby.
The recommendation that women be vaccinated against pertussis in every pregnancy – using the Tdap vaccine here in the U.S. – was new in 2012. It wasn’t recommended when I was pregnant with Cee in 2010, although I had recently gotten a Tdap booster for my job at the time. Several pregnant friends and readers have emailed me this fall asking if Tdap in pregnancy is safe and if they really need it, particularly if they were just vaccinated in the last couple of years. The good news is that there have been quite a few studies published on these questions in just the last year or two, and I’ll focus the rest of this post on the evidence for the Tdap shot in pregnancy.
What is the concern about pertussis in young infants?
We’ve seen big increases in pertussis recently, especially over the last decade. In 2012, there were more than 48,000 cases reported in the U.S., making it the worst year since 1955. Pertussis hits young infants the hardest. Among the 20 deaths from pertussis in the U.S. in 2012, 15 were in infants less than 3 months of age [PDF]. The first dose of pertussis vaccine is usually given with the DTaP shot at 2 months of age, and before this time, infants are particularly vulnerable to the disease. The 2012 recommendation that women be vaccinated with Tdap in the third trimester of every pregnancy came in response to these infant deaths, the hope being that maternal antibodies to pertussis could help protect infants during those first few months of life.
Previous to the recommendation to vaccinate during pregnancy, pertussis prevention strategies were focused on “cocooning” infants. That meant vaccinating women just after giving birth and also trying to vaccinate family members and others around them to decrease newborns’ exposure to pertussis. While this strategy made sense, research has shown that it isn’t particularly effective at protecting infants from pertussis. It can take several weeks for pertussis antibodies to peak in moms after vaccination, leaving mom and baby vulnerable during the first few weeks postpartum, and it can be challenging (and expensive) to get everyone in contact with the baby vaccinated. It certainly doesn’t hurt to ensure that the family is up-to-date on their pertussis vaccines, and some studies suggest that it helps a little, but overall, it’s turned out to be a pretty inefficient strategy. Tara Haelle reviewed some of the latest research on cocooning here.
Is there evidence that Tdap vaccination in pregnancy can protect babies from pertussis?
The strategy of vaccinating moms during pregnancy takes advantage of the natural transfer of mom’s antibodies to the fetus across the placenta. Several recent studies show that this is an effective way to boost baby’s immunity. Given the pertussis outbreaks in recent years and the finding that cocooning offers only minor protection, this is pretty great news.
A small randomized controlled trial led by Flora Munoz of Baylor College of Medicine, published in JAMA in May of this year, gave 33 women Tdap and 15 women a placebo at 30-32 weeks of pregnancy.5 After giving birth, the treatments were crossed over so that the women receiving the vaccine during pregnancy received the placebo postpartum and vice versa. Predictably, the moms who received the vaccine during pregnancy had higher antibody levels in their blood at the time of delivery, and this was also reflected in their infants at birth and at 2 months of age. Researchers measured antibodies to 4 different proteins produced by the Bordatella pertussis bacterium, and depending on the protein, levels were 5x-36x higher in infants whose moms were vaccinated in pregnancy compared to those who weren’t.
Although the Munoz study was small, it very convincingly demonstrated that vaccination in pregnancy confers greater anti-pertussis antibodies to infants. What it couldn’t do was tell us whether these antibody levels actually protect infants from pertussis infection in the first few months of life. To answer this question, we need much larger groups of study subjects, which means turning to epidemiological studies.
That’s where a study from the U.K., published in the Lancet in October of this year, comes in.6 As in the U.S., there was a huge pertussis outbreak in the U.K. in 2012, during which 14 infants died. In September of that year, the U.K. Department of Health recommended that pregnant women receive the acellular pertussis vaccine between 28 and 38 weeks of pregnancy. In the subsequent year, about 60% of pregnant women were vaccinated.
The Lancet study tracked confirmed pertussis cases occurring in infants younger than 3 months before and after this new recommendation and then looked back at their mothers’ vaccination records to see if vaccination in pregnancy affected their chances of infection.6 The results were impressive. Of 82 pertussis cases in young infants, most were born to women who didn’t receive the vaccine during pregnancy. Only 12 of them (15%) were born to mothers vaccinated at least one week before giving birth. The researchers calculated that the pertussis vaccine was 91% effective in preventing pertussis in young infants, so long as it was given at least 7 days before birth. If the vaccine was given less than 7 days before birth or in the immediate postpartum period, vaccine effectiveness dropped to 38%.
This last part about the timing of the vaccine is important, and it explains in part why the recommendation is to receive the vaccine during the third trimester of every pregnancy. After vaccination, it takes a couple of weeks for anti-pertussis antibodies to peak in the mom,7,8 which is why it is important to vaccinate well before your due date. However, it’s also important not to vaccinate too early. After the antibody peak, circulating pertussis antibodies seem to drop pretty quickly. When women are vaccinated before pregnancy or early in pregnancy, the pertussis antibody concentrations found in cord blood appear to be too low to provide much protection to the infant and are much lower than those found in women vaccinated in the third trimester.5,9 (This doesn’t mean that mom can’t mount an effective immune response to pertussis if exposed, just that circulating antibodies available to cross the placenta are low.) In general, maternal IgG antibodies are not transported across the placenta very efficiently until the third trimester, so to optimize placental transfer to the baby, we want mom’s antibody concentrations to peak during that time.10
Maternal vaccination during pregnancy is an elegant solution to the problem of this deadly disease in newborns. It allows us to give mom a small, controlled dose of inactivated pertussis toxoids at an optimal time in late pregnancy, and the baby gets the benefit of being born with at least temporary immunity to pertussis, enough to protect her during early infancy until she can receive her own vaccine around 2 months.
Is there evidence that Tdap vaccination in pregnancy is safe for the mom and baby?
Two studies out this year provide reassuring data on the safety of Tdap in pregnancy. Tara Haelle (again!) wrote about both of these here and here, so I’ll mention these findings only briefly. A U.K. study, published in the BMJ in July, compared pregnancy and birth outcomes in more than 20,000 women who received the pertussis vaccine in the third trimester to a matched group of unvaccinated pregnant women.11 There were no differences between the vaccinated and unvaccinated groups when it came to risk of stillbirth, maternal or neonatal death, pre-eclampsia or eclampsia, hemorrhage, fetal distress, uterine rupture, placenta or vasa previa, cesarean birth, low birth weight, or neonatal renal failure.
A more recent study, published last month in JAMA, looked back at more than 123,000 women in California’s Kaiser health system, 21% of whom had received Tdap during pregnancy.12 In this study, there were no differences in risk of small-for-gestational age birth, preterm birth, or hypertensive disorders in pregnancy between vaccinated and unvaccinated women. Vaccinated women were slightly more likely to be diagnosed with chorioamnionitis (6.1%), a bacterial infection of the fetal membranes, compared with unvaccinated women (5.5%). Tara Haelle explained why we shouldn’t freak out about that finding in her post on the study (the association is likely due to confounding factors that weren’t considered in the study).
Finally, the randomized controlled trial conducted by Munoz et al, which included the antibody data mentioned earlier, also included a detailed assessment of reactions to the vaccine as well as birth and baby outcomes.5 This study found no difference in birth weight, gestational age, Apgar scores, neonatal exams, birth complications, or the baby’s growth and development later in infancy. Pain at the injection site of Tdap was common – occurring in about 3 out of 4 women – and more frequent than found in the placebo group, but symptoms were generally mild and resolved on their own within a few days. (This was also my experience – a sore arm for a couple of days.)
What’s the bottom line? Receiving the Tdap vaccine during the third trimester of pregnancy is our best chance at protecting young infants from pertussis, a disease that can be particularly dangerous during the first few months of life. Research shows that vaccination in late pregnancy gives newborns the gift of pertussis-specific antibodies at birth and is safe for both mother and baby.
- Keener, A. B. Efficacy studies build up the case for prenatal immunization. Nat. Med. 20, 970–972 (2014).
- Steinhoff, M. C. et al. Influenza Immunization in Pregnancy — Antibody Responses in Mothers and Infants. N. Engl. J. Med. 362, 1644–1646 (2010).
- Zaman, K. et al. Effectiveness of Maternal Influenza Immunization in Mothers and Infants. N. Engl. J. Med. 359, 1555–1564 (2008).
- Benowitz, I., Esposito, D. B., Gracey, K. D., Shapiro, E. D. & Vázquez, M. Influenza Vaccine Given to Pregnant Women Reduces Hospitalization Due to Influenza in Their Infants. Clin. Infect. Dis. 51, 1355–1361 (2010).
- Munoz FM, Bond NH, Maccato M & et al. Safety and immunogenicity of tetanus diphtheria and acellular pertussis (tdap) immunization during pregnancy in mothers and infants: A randomized clinical trial. JAMA 311, 1760–1769 (2014).
- Amirthalingam, G. et al. Effectiveness of maternal pertussis vaccination in England: an observational study. The Lancet 384, 1521–1528 (2014).
- Kirkland, K. B., Talbot, E. A., Decker, M. D. & Edwards, K. M. Kinetics of Pertussis Immune Responses to Tetanus-Diphtheria-Acellular Pertussis Vaccine in Health Care Personnel: Implications for Outbreak Control. Clin. Infect. Dis. 49, 584–587 (2009).
- Halperin, B. A. et al. Kinetics of the Antibody Response to Tetanus-Diphtheria-Acellular Pertussis Vaccine in Women of Childbearing Age and Postpartum Women. Clin. Infect. Dis. 53, 885–892 (2011).
- Healy, C. M., Rench, M. A. & Baker, C. J. Importance of timing of maternal combined tetanus, diphtheria, and acellular pertussis (Tdap) immunization and protection of young infants. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 56, 539–544 (2013).
- Glezen, W. P. & Alpers, M. Maternal immunization. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 28, 219–224 (1999).
- Donegan, K., King, B. & Bryan, P. Safety of pertussis vaccination in pregnant women in UK: observational study. BMJ 349, g4219–g4219 (2014).
- Kharbanda EO, Vazquez-Benitez G, Lipkind HS & et al. Evaluation of the association of maternal pertussis vaccination with obstetric events and birth outcomes. JAMA 312, 1897–1904 (2014).