Safety of influenza vaccination during pregnancy: a systematic review. 2023

Dianna M Wolfe, and Deshayne Fell, and Chantelle Garritty, and Candyce Hamel, and Claire Butler, and Mona Hersi, and Nadera Ahmadzai, and Danielle B Rice, and Leila Esmaeilisaraji, and Alan Michaud, and Charlene Soobiah, and Marco Ghassemi, and Paul A Khan, and Angela Sinilaite, and Becky Skidmore, and Andrea C Tricco, and David Moher, and Brian Hutton
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

We conducted a systematic review to evaluate associations between influenza vaccination during pregnancy and adverse birth outcomes and maternal non-obstetric serious adverse events (SAEs), taking into consideration confounding and temporal biases. Electronic databases (Ovid MEDLINE ALL, Embase Classic+Embase and the Cochrane Central Register of Controlled Trials) were searched to June 2021 for observational studies assessing associations between influenza vaccination during pregnancy and maternal non-obstetric SAEs and adverse birth outcomes, including preterm birth, spontaneous abortion, stillbirth, small-for-gestational-age birth and congenital anomalies. Studies of live attenuated vaccines, single-arm cohort studies and abstract-only publications were excluded. Records were screened using a liberal accelerated approach initially, followed by a dual independent approach for full-text screening, data extraction and risk of bias assessment. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence certainty. Of 9443 records screened, 63 studies were included. Twenty-nine studies (24 cohort and 5 case-control) evaluated seasonal influenza vaccination (trivalent and/or quadrivalent) versus no vaccination and were the focus of our prioritised syntheses; 34 studies of pandemic vaccines (2009 A/H1N1 and others), combinations of pandemic and seasonal vaccines, and seasonal versus seasonal vaccines were also reviewed. Control for confounding and temporal biases was inconsistent across studies, limiting pooling of data. Meta-analyses for preterm birth, spontaneous abortion and small-for-gestational-age birth demonstrated no significant associations with seasonal influenza vaccination. Immortal time bias was observed in a sensitivity analysis of meta-analysing risk-based preterm birth data. In descriptive summaries for stillbirth, congenital anomalies and maternal non-obstetric SAEs, no significant association with increased risk was found in any studies. All evidence was of very low certainty. Evidence of very low certainty suggests that seasonal influenza vaccination during pregnancy is not associated with adverse birth outcomes or maternal non-obstetric SAEs. Appropriate control of confounding and temporal biases in future studies would improve the evidence base.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007251 Influenza, Human An acute viral infection in humans involving the respiratory tract. It is marked by inflammation of the NASAL MUCOSA; the PHARYNX; and conjunctiva, and by headache and severe, often generalized, myalgia. Grippe,Human Flu,Human Influenza,Influenza in Humans,Influenza,Flu, Human,Human Influenzas,Influenza in Human,Influenzas,Influenzas, Human
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000022 Abortion, Spontaneous Expulsion of the product of FERTILIZATION before completing the term of GESTATION and without deliberate interference. Abortion, Tubal,Early Pregnancy Loss,Miscarriage,Spontaneous Abortion,Abortions, Spontaneous,Abortions, Tubal,Early Pregnancy Losses,Loss, Early Pregnancy,Losses, Early Pregnancy,Miscarriages,Pregnancy Loss, Early,Pregnancy Losses, Early,Spontaneous Abortions,Tubal Abortion,Tubal Abortions
D047928 Premature Birth CHILDBIRTH before 37 weeks of PREGNANCY (259 days from the first day of the mother's last menstrual period, or 245 days after FERTILIZATION). Preterm Birth,Birth, Premature,Birth, Preterm,Births, Premature,Births, Preterm,Premature Births,Preterm Births
D050497 Stillbirth The event that a FETUS is born dead or stillborn. Stillbirths
D053118 Influenza A Virus, H1N1 Subtype A subtype of INFLUENZA A VIRUS with the surface proteins hemagglutinin 1 and neuraminidase 1. The H1N1 subtype was responsible for the Spanish flu pandemic of 1918 and 2009 H1N1 pandemic. H1N1 Influenza Virus,H1N1 Virus,H1N1 subtype,H1N1v Viruses,Influenza A (H1N1)pdm09,Influenza A (H1N1)pdm09 Virus,Influenza A H1N1, Variant Virus,Swine-Origin Influenza A H1N1 Virus,H1N1 Influenza Viruses,H1N1 Viruses,H1N1 subtypes,H1N1v Virus,Influenza Virus, H1N1,Swine Origin Influenza A H1N1 Virus,Virus, H1N1,Virus, H1N1 Influenza,Virus, H1N1v,subtype, H1N1

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