10,000 pregnant women given flu vaccines: What happened next

The article, written by a team led by Paul Loubet of France’s Université de Montpellier, cited three large randomised controlled trials in South Africa, Mali and Nepal. The studies were conducted between 2011 and 2014. The research projects, funded by the Bill & Melinda Gates Foundation, sought to increase the evidence base for the effects of maternal influenza immunisation. The article was co-authored by Vassilis Tsatsaris of the Maternité Port-Royal in Paris, and Odile Launay of Paris-based Réseau Innovative Clinical Research in Vaccinology.

What did the trials show?

These large randomised controlled trials showed that inactivated influenza vaccine (IIV) was effective in preventing lab-confirmed influenza (confirmation via polymerase chain reaction, PRC, test) in pregnant women and in infants younger than 6 months.

One important section of the trial, the part conducted in Nepal, showed that maternal immunisation reduced the frequency of low birthweight infants by 15%. The Lancet article cited researcher Saad B Omer and colleagues as reporting the pooled analysis of these three trials, which included 10,002 pregnant women (5,017 assigned to IIV and 4,985 assigned to “control”) and 9,800 liveborn infants (4,910 livebirths from women who received IIV, and 4,890 livebirths from women who received control). Together, the studies represented the largest dataset on women and newborns concerning influenza immunisation during pregnancy.

Why is flu vaccine uptake notoriously low?

Influenza vaccine avoidance is quite high — even among high-risk groups. It's down to unfounded fears, or lack of understanding, say experts. There are plenty of conspiracy theories surrounding vaccines, now magnified by hyper-sharing on social media. And while the world is still scrambling to find a lifesaving vaccine against SARS-CoV-2, there's an approved vaccine against the influenza virus already.

One reason for vaccine hesitancy comes from a false belief among some, i.e. "I never get the flu". Then there's the noisy tribe of anti-vaxxers peddling unsubstantiated fears, or outright lies, that the jab would actually give you the flu.

The plain reality is this: nobody wants to go through the pain of an intramuscular shot. But the alternative is unimaginably worse — entire communities beset by polio, tetanus, rubella, measles, rabies, hepatitis A&B, the brain-wasting Hib, pertussis, diptheria, rotavirus, pneumococcal disease, mumps, chickenpox and, of course, influenza (flu). These diseases had been controlled significantly, thanks to vaccines developed by generations of scientists working together for decades.

How long did flu vaccine efficacy last?

First, the studies show that trivalent IIV administered at any time during pregnancy is effective in protecting pregnant women against PCR-confirmed influenza with a vaccine efficacy of 42% (and with a 95% confidence interval) during pregnancy and 60% in the postpartum period.

The study found that efficacy lasted until 6 months after vaccination, at 49% of cases (with a 95% confidence interval). Following the mother's immunisation, it appears to be effective in protecting infants up to 6 months of age, at a vaccine efficacy of 35% [with 95% CI] on cumulative episodes of PCR-confirmed influenza. 

What are the implications?

The Lancet cited two: First, it supports the immunisation strategy of based on the passive transplacental transfer of anti-influenza antibodies, which allows for effective protection of children who cannot be vaccinated against influenza [because influenza vaccines are not approved in children 0–6 months old].

Second, it shows that there is a period between the ages of 4 months (disappearance of maternal antibodies) and 6 months (possible start of vaccination) when children are no longer protected, which should be considered in immunisation strategies based on recombinant or high dose or adjuvanted influenza vaccines during pregnancy.

Moreover, in this pooled data, the vaccine was not effective against influenza B in infants (vaccine efficacy 13%, 95% CI −21 to 37). This finding could be explained by the frequent mismatch between vaccine and circulating influenza B strains in trivalent IIV.

What about the effects of quadrivalent IIV in pregnant women?

Researchers said further studies are recommended on the use of the quadrivalent IIV in pregnant women, which would probably improve the overall vaccine efficacy and the efficacy against influenza B, especially in children.

When is the best time to get a flu shot during pregnance?

The Lancet article said the large-scale data set found no difference in efficacy against PCR-confirmed influenza in infants when the mothers were vaccinated before or after 29 weeks of gestation. 

What about the safety of seasonal flu shots during pregnancy?

Researchers concluded that, based on the study results, they confirmed that seasonal influenza vaccination during pregnancy is safe. There are two important points of safety — for both the mother and fetus. Studies show there’s no increased incidence of adverse events in mothers.

More importantly, the flu shots posed no safety issues for fetuses and newborns — when considering low birthweight, stillbirth, preterm birth, and small for gestational age as measures. In the trials in Bangladesh and Nepal, it what was suggested the pooled data show no positive association between maternal immunisation and low birthweight.

“These findings would be a strong argument for recommending generalised maternal influenza immunisation in resource-limited countries and suggest that further research considering the heterogeneity of the findings across countries is needed,” the researchers stated.

Why is getting a flu vaccine more important during COVID times?

Health authorities around the world stress that getting a flu vaccine is more important than ever during 2020-2021 to protect yourself and the people around you from flu. Moreover, it helps reduce the strain on healthcare systems responding to the COVID-19 pandemic.

What accounts for fears or myths about the flu vaccine during pregnancy?

There are several reasons: First, the anti-vaccine movement has suspected a "link" between the H1N1 version of the flu vaccine during the first trimester of pregnancy and autism spectrum disorder diagnosis in the child in later life. It was a suspicion and no evidence was cited.

But this suspicion was addressed by a large-scale study released in August 2020 by researchers at Karolinska Institutet in Sweden, published in the Annals of Internal Medicine journal.

Second, the most common fear — that the vaccine itself will give you the flu — comes from a misconception. Here's one simple, but important fact: The flu vaccine will not cause flu because the vaccine contains non-infectious (inactivated) particles of the virus. In other words, it's a "killed" flu virus, a tried-and-tested platform in making vaccines. It merely alerts the body to the threat of the virus.

What about those who develop flu-like symptoms?

A small minority of people might develop flu-like symptoms (mild fever and muscle aches after vaccination). These are considered as minor side effects and are not the same as fullblown influenza infection. Immunity against influenza does not develop until 1 – 2 weeks after vaccination. So if you catch the flu post-vaccine, it’s possible that you were exposed to the influenza viruses before getting the benefit from the vaccine. Sometimes it can also be difficult to tell the differences between flu and common cold. Both are respiratory illnesses, and may have similar symptoms but both are caused by different types of viruses. The flu vaccine only protects against certain influenza viruses.

Who are most at risk of serious complications with flu?

What’s the takeaway?

Pooled data from different countries involved in the massive study confirm that flu vaccines during pregnancy is safe and effective for protecting both mothers and fetuses. Mothers can have more confidence and decide based on scientific facts, instead of a suspicions or be a victim of disinformation/