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# Influenza immunisation in pregnancy is efficacious and safe, but questions remain

Paul Loubet, Vassilis Tsatsaris, Odile Launay

► To cite this version:

Paul Loubet, Vassilis Tsatsaris, Odile Launay. Influenza immunisation in pregnancy is efficacious and safe, but questions remain. The Lancet Respiratory Medicine, 2020, 8 (6), pp.533-534. 10.1016/S2213-2600(20)30034-5. hal-02958974

HAL Id: hal-02958974

https://hal.umontpellier.fr/hal-02958974

Submitted on 6 Oct 2020

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Distributed under a Creative Commons Attribution 4.0 International License
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Influenza immunisation in pregnancy is efficacious and safe,
but questions remain

oa
OPEN ACCESS

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CrossMark

Pregnant women and infants are at high risk of severe influenza.¹,² Since 2012, WHO has recommended influenza immunisation during pregnancy in any trimester and targets pregnant women as a high priority in annual influenza vaccination programmes. Although trivalent seasonal inactivated influenza vaccine (IIV) has shown efficacy against influenza infections in both pregnant women and infants,³,⁴ the optimal timing of vaccination and effect on infant outcomes and safety remain controversial. The Bill & Melinda Gates Foundation funded three large randomised controlled trials in South Africa, Mali, and Nepal, which were done between 2011 and 2014, to increase the evidence base for the effects of maternal influenza immunisation.⁵⁻⁷ The three trials showed that IIV was effective in preventing laboratory-confirmed influenza in pregnant women and in infants younger than 6 months. In the trial done in Nepal, maternal immunisation reduced the frequency of low birthweight infants by 15%.

In *The Lancet Respiratory Medicine*, Saad B Omer and colleagues⁸ report the pooled analysis of these three trials, which included 10 002 pregnant women (5017 assigned to IIV and 4985 assigned to control) and 9800 liveborn infants (4910 livebirths from women who received IIV, and 4890 livebirths from women who received control) representing the largest dataset on women and newborns concerning influenza immunisation during pregnancy.

Several lessons can be learned from the results of Omer and colleagues' study. First, trivalent IIV administered at any time during pregnancy is effective in protecting pregnant women against PCR-confirmed influenza with a vaccine efficacy of 42% (95% CI 12–61) during

pregnancy and 60% (36–75) in the postpartum period.
Efficacy lasted until 6 months after vaccination (49%,
95% CI 29–63), which has implications for countries
with year-round influenza virus circulation.

Second, although maternal immunisation appears to be effective in protecting infants up to 6 months of age (vaccine efficacy 35% [95% CI 19 to 47] on cumulative episodes of PCR-confirmed influenza), this protection is significant only up to 4 months of age (56% [28 to 73] before 2 months and 39% [11 to 58] between 2 and 4 months) but not between 4 and 6 months of age (19%, 95% CI -9 to 40) underscoring the progressive decline in maternal antibody titre. This finding has two implications. First, it supports the immunisation strategy 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 analysis, 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. Research on the use of the quadrivalent IIV in pregnant women, which would probably improve the overall vaccine efficacy and the

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Microgen Images/Science Photo Library

See Articles page 597
efficacy against influenza B, especially in children, is
therefore warranted.

Third, the optimal timing of immunisation during
pregnancy remains unclear. Whether the gestational
stage of pregnancy affects responses to vaccines has not
yet been extensively studied and conflicting results on
seroconversion after seasonal influenza immunisation
exist. In this study, there was no difference in efficacy
against PCR-confirmed influenza in infants when the
mothers were vaccinated before or after 29 weeks
of gestation. Concerning the mothers, there was no
efficacy against PCR-confirmed influenza when they
were vaccinated before 29 weeks gestational age
(vaccine efficacy 30%, 95% CI -2 to 52). As explained
by the authors, this absence of efficacy in mothers
vaccinated before 29 weeks gestational age is probably
due to statistical considerations (lack of power), rather
than a real difference in efficacy, as this would be
inconsistent with studies that have shown a waning
serological response to influenza immunisation as
pregnancy progresses.⁹

Fourth, these results confirm that seasonal influenza
vaccination during pregnancy is safe. In addition
to studies that did not show an increased incidence
of adverse events in mothers,³ safety in fetuses and
newborns was also shown when considering low
birthweight, stillbirth, preterm birth, and small for
gestational age. However, contrary to what was
suggested in the trials in Bangladesh⁴ and Nepal,⁷ 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.

In conclusion, these pooled data confirm that
influenza immunisation during pregnancy is safe and

effective for protecting both women and infants.
Further research is warranted to consider more
immunogenic vaccines to fill the protection gap in
infants between 4 and 6 months of age and improve
understanding of the association between maternal
immunisation and child weight and length at birth at
6 months of age.

PL has received personal fees and non-financial support from Pfizer and Sanofi Pasteur. VT has received personal fees from Alexion and grants and personal fees from Roche Diagnostics and is a member of the scientific board of Obseva. OL has received personal fees from Sanofi Pasteur, grants, personal fees, and non-financial support from Pfizer, Janssen, and Sanofi Pasteur-Merck Sharp & Dohme, and grants, and non-financial support from GlaxoSmithKline.

Paul Loubet, Vassilis Tsatsaris, *Odile Launay

odile.launay@aphp.fr

VBMI, INSERM U1047, Université de Montpellier, Service des Maladies Infectieuses et Tropicales, CHU Nîmes, Nîmes, France (PL); Inserm, F-CRIN, Réseau Innovative Clinical Research in Vaccinology, Paris, France (PL, OL); Maternité Port-Royal (VT), FHU PREMA (VT, OL), and Inserm, CIC Cochin Pasteur (OL), Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris 75014, France (OL); and Université de Paris, Paris, France (OL)

© The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license.

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6. Tapia MD, Sow SO, Tamboura B, et al. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial. *Lancet Infect Dis* 2016; **16**: 1026-35.

7. Steinhoff MC, Katz J, Englund JA, et al. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. *Lancet Infect Dis* 2017; **17**: 981-89.

8. Omer SB, Clark DR, Madhi SA, et al. Efficacy, duration of protection, birth outcomes, and infant growth associated with influenza vaccination in pregnancy: a pooled analysis of three randomised controlled trials. *Lancet Respir Med* 2020; **8**: 597-608.

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CrossMark

Challenges in the interpretation and application of typical
imaging features of COVID-19

Published Online
May 18, 2020
https://doi.org/10.1016/
S2213-2600(20)30233-2

The detailed report by Timothy Harkin and colleagues¹ of
an unusual case of respiratory illness eventually diagnosed
as COVID-19 raises issues about the role of imaging in the

management of the disease. The causative virus, severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
can result in lethal pneumonia, so might chest imaging