Maternal Tdap vaccination during pregnancy is not associated with autism in the child

If there’s one idée fixe among antivaxers (besides the long disproven ideas that vaccine cause autism and a large number of bad health consequences, or, as I like to call it, “It’s always the vaccines—always”), it’s utter horror that the CDC and medical profession would recommend that pregnant women be vaccinated against certain diseases. For instance, antivaccine ideologues are utterly convinced that the flu vaccine, when administered to pregnant women, causes miscarriages when it does not and in fact, one outlier study to the contrary, the overwhelming preponderance of evidence supports the conclusion that vaccinating pregnant women against the flu vaccine is safe and effective and protects a vulnerable population (pregnant women) from the adverse consequences of the flu. In fact, if anything, vaccinating against influenza during pregnancy is associated with lower rates of stillbirth, neonatal death, and premature delivery as well as lower risk of the flu in the infant. Of course, antivaxers hate the CDC recommendation to vaccinate pregnant women against pertussis using the Tdap combination vaccine. It’s already been shown that doing so is safe in terms of not increasing the risk of stillbirth, premature delivery, maternal or neonatal death, pre-eclampsia or eclampsia, haemorrhage, fetal distress, uterine rupture, placenta or vasa praevia, caesarean delivery, low birth weight, or neonatal renal failure. But what about autism? Well, thanks to a new study, we have good evidence that maternal Tdap vaccination during pregnancy doesn’t increase the risk of autism in the baby either.

The evidence comes in the form of a study published earlier this week in Pediatrics from a group based at Kaiser Permanente Southern California led by Tracy Becerra-Culqui, which provides robust evidence that vaccinating the mother during pregnancy does not place the baby at a higher risk for autism.

The Tdap vaccine, of course, contains vaccines against tetanus, diphtheria and pertussis, the last of which causes whooping cough. In order to protect the mother and baby, the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the American College of Nurse-Midwives all encourage expectant mothers to get the Tdap vaccine in the third trimester of pregnancy to protect their babies from pertussis.

The authors summarize the rationale in the introduction:

Prenatal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap) vaccination has been shown to be effective in protecting vulnerable young infants from pertussis. Prompted by waning immunity, pertussis incidence has risen in the past decade in the United States, with peaks in 2010 and 2014.1,2 Young infants are at the highest risk of hospitalization and death after pertussis infection, a highly contagious respiratory disease (whooping cough) caused by the bacterium Bordetella pertussis.3 In response, in October 2011 the Advisory Committee on Immunization Practices (ACIP) recommended that unvaccinated pregnant women receive the Tdap vaccine after 20 weeks’ gestation.4 Given the seriousness of the matter, this recommendation was amended in October 2012 to include all pregnant women regardless of previous vaccinations, and the optimal vaccination period was defined between 27 and 36 weeks’ gestation.5 Evidence revealed that antibodies are passed along to newborns, and the vaccine was 91.4% effective in providing some immunity until newborns reach 2 months of age, the age they are expected to receive their first dose of the diphtheria-tetanus-acellular pertussis vaccine.6,7 Given the increasing practice to vaccinate pregnant women with Tdap, it is important to address the concern of a potential link between maternal vaccination and subsequent development of autism spectrum disorder (ASD) in children.

At the risk of sounding as though I’m advocating “suppressing research,” I can’t help but point out right here that this is a study that probably didn’t need to be done, at least not from a strictly scientific basis. There’s no known mechanism and no good preliminary data to suggest that there might be a link between prenatal vaccination with Tdap and the subsequent development of autism. Again, this is a study that was done primarily because antivaxers keep agitating and spreading misinformation that vaccines cause autism rather than from any compelling scientific rationale. I suppose you can justify the study because of the lack of evidence regarding long term effects of Tdap vaccination of pregnant mothers on the risk of autism in their offspring, but mechanistically speaking it’s not a super compelling justification. But, as I say, I’ll allow it.

Now one of the great things about Kaiser Permanente is that it has a unified electronic medical record from which information very useful for doing epidemiological studies can be readily extracted and analyzed. Couple that with a large number of members (over four million), and you have a very nice source to mine looking for correlations between vaccination and adverse outcomes. This particular study was a retrospective cohort study that looked at the outcome of a diagnosis of an autism spectrum disorder in children all Kaiser Permanente Southern California (KPSC) hospitals born between January 1, 2011 and December 31, 2014. The authors note that all recommended immunizations are free to members, regardless of the specific copayment required by the Kaiser plan to which they belong.

Eligibility was restricted to pregnant women who had not undergone in vitro fertilization to get pregnant and who delivered live singleton infants between 22-45 weeks’ gestation. Because of KPSC’s electronic medical record, the children’s medical records were linked longitudinally using unique identifiers. Children with chromosomal or congenital anomalies were excluded. Maternal Tdap vaccination was captured from the EMR and defined as receipt of the vaccine during any point during the pregnancy, and an ASD was defined by a clinical diangosis any time after turning one year of age as recorded in the EMR between January 1, 2012 and June 30, 2017.

Naturally, a number of potentially confounding factors were incorporated into the analysis, such as maternal age, race and/or ethnicity, language, educational attainment, medical center of delivery, type of health insurance, parity, receipt of influenza vaccine during pregnancy, start of prenatal care, and medical complications of pregnancy, such as pregestational hypertension, preeclampsia or eclampsia, pregestational and gestational diabetes, placenta previa, and placental abruption. Children were followed from birth to first ASD diagnosis, end of membership in the health plan, or the end of the study follow-up period, whichever came first. Age of ASD diagnosis, and the incidence rate of ASD diagnosis by Tdap vaccination status were calculated.

Here’s a flowsheet for the study:

Study flow sheet

Study flow sheet

The authors found that Tdap vaccination coverabge ranged from 26% for the 2012 birth cohort to 79% for the 2014 birth cohort, which to me represents a very impressive increase in Tdap coverage over just a three year period. The mean gestational age at vaccination was 28 weeks, and women vaccinated during pregnancy were more likely to be Asian-American or Pacific Islander, have a bachelor’s degree or higher, be nulliparous, have received the influenza vaccine prenatally, and give birth at term (≥37 weeks’ gestation) compared with unvaccinated women.

The raw data showed that 569 children (1.5%) whose mothers received the vaccination were later diagnosed with autism, compared with 772 children (1.8%) whose mothers did not get the shot. Overall, the ASD incidence rate was 3.78 per 1,000 person-years in the group who received the Tdap, while it was 4.05 per 1,000 person-years in the unvaccinated group. The unadjusted hazard ratio was 0.98. After accounting for the various confounders in an analysis known as propensity score weighting, the adjusted hazard ratio was 0.85 (95% confidence interval: 0.77-0.95), which means that the risk of ASD in children of mothers vaccinated with Tdap during pregnancy was actually slightly lower than in the unvaccinated. However, the authors were cautious and simply concluded that their study didn’t provide any evidence of increased risk of ASD associated with prenatal vaccination with Tdap, which is an appropriate way to interpret the data. That doesn’t however, mean that they don’t allude to it in the discussion:

In this large retrospective observational cohort study of 81,993 pairs of diverse pregnant women and their children, we found no evidence of increased risk for ASD diagnosis associated with Tdap vaccination during pregnancy. Subanalyses supported the overall results, revealing minimal variability by year of birth and parity. No study to our knowledge has been published with results examining the risk of ASD after maternal exposure to the Tdap vaccine.

Maternal immune activation during pregnancy is hypothesized to indirectly affect fetal neurodevelopment.32–35 Researchers have found infections during pregnancy (eg, rubella and influenza), including prolonged episodes of fever to increase autism risk, hypothesizing that maternal infections, cytokine responses, and proinflammatory pathways are likely to alter fetal brain development.32,36–41 Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.

The study is not perfect, obviously. For one thing, it’s retrospective and thus prone to all the biases and shortcomings to which such studies are inherently prone. However, the authors did a good job controlling for those biases. Another issue was that ASD status was determined by diagnoses recorded in the EMR and was not confirmed by a study-specific standardized assessment. However, they also note that ASD diagnoses were also likely captured consistently during most of the study years because of a California law (Senate Bill 946) that require health plans to cover ASD-related health costs, such as diagnostic and behavioral health treatment, which led to the implementation of systematic procedures for screening and diagnosing within the KPSC health care system. That means that an ASD diagnosis can only be made by a qualified mental health professional. The authors also note that the combined prevalence of ASD in their study was 1.6%, indistinguishable from the 1.7% prevalence reported in the US among eight-year-old children.

There were strengths, as well. One strength is that maternal Tdap vaccination and ASD information were not subject to recall bias, and weighting procedures enabled investigators to balance Tdap exposed and unexposed groups statistically. Also, children whose first ASD diagnosis was before age 2 also had a diagnosis after age 2, which aligns with the American Academy of Pediatrics autism screening recommended schedule of 18- and 24-months.

The bottom line is that, as is the case with every well-designed study of vaccines and autism, this study is yet another negative study. There isn’t even a whiff of a hint of a whisper of a correlation between maternal Tdap vaccination and autism in the mother’s child. Same as it ever was for every other vaccine tested and autism.