Introduction: Adverse intrauterine conditions, including maternal infection, may negatively influence offspring development, potentially leading to adverse outcomes later in life. Although the perinatal impact of influenza infection during pregnancy has been reviewed, comprehensive assessment of the evidence on the effect of maternal influenza infection on childhood outcomes, beyond infancy, has not been performed. The objective of this systematic review was to assess the association between influenza infection in utero and development of adverse health outcomes in offspring beyond six months.
Methods: Records were extracted from MEDLINE, EMBASE, CINAHL and Web of Science databases, from inception to 2 July 2019. Two independent reviewers extracted the data and assessed methodological quality. Studies reporting health outcomes, beyond six months of age, comparing offspring born to women with and without influenza infection during pregnancy were considered for inclusion. We excluded non-English studies, case reports or series, systematic, narrative or literature reviews, editorials, letters to the editor, commentaries, animal studies, and conference abstracts.
Results: A total of 67 articles were included, comprising various study designs including case-control (n=14), ecological (n=15), nested case-control (n=9), prospective cohort (n=9), and retrospective cohort (n=20). Eighteen studies were published in 2010 or later, thirty-five between 1990 and 2009, and eleven prior to 1990. Studies ascertained maternal influenza infection through ecologic (i.e., pregnancy aligned with influenza season; n=32), self-report (n=17), ICD-9/ICD-10 diagnostic codes (n=8), laboratory confirmation (n=5), and other methods (e.g. chart review; n=5). Most articles originated from Europe (n=44) and North America (n=15). Mental, behavioural and neurodevelopmental disorders were investigated in forty studies, with schizophrenia being the most frequently reported (n=20).
Conclusion: This ongoing review will provide a comprehensive assessment of evidence on potential long-term health consequences for offspring exposed to influenza infection in utero. These findings may have implications for prevention and invention strategies and will identify evidence gaps requiring future research.
Georgia Condran– Undergraduate Student, Acadia University, Wolfville, NS
Annette Regan– Assistant Professor, School of Public Health, Texas A & M University, USA; School of Public Health, Curtin University, Perth, Australia
Christina Ricci– MPH Candidate, Dalla Lana School of Public Health, University of Toronto
Damien Foo– PhD Candidate, School of Public Health, Curtin University, Perth, Australia
Minda Sarna– Research Fellow, School of Public Health, Curtin University, Perth, Australia
Deshayne Fell– Assistant Professor & Scientist, Children’s Hospital of Eastern Ontario (CHEO) Research Institute; School of Epidemiology and Public Health, University of Ottawa; ICES, Toronto and Ottawa