Maternal influenza and birth outcomes: systematic review of comparative studies

Abstract

BackgroundAlthough pregnant women are considered at high risk for severe influenza disease, comparative studies of maternal influenza and birth outcomes have not been comprehensively summarised.ObjectiveTo review comparative studies evaluating maternal influenza disease and birth outcomes.Search strategyWe searched bibliographic databases from inception to December 2014.Selection criteriaStudies of preterm birth, small‐for‐gestational‐age (SGA) birth or fetal death, comparing women with and without clinical influenza illness or laboratory‐confirmed influenza infection during pregnancy.Data collection and analysisTwo reviewers independently abstracted data and assessed study quality.Main resultsHeterogeneity across 16 studies reporting preterm birth precluded meta‐analysis. In a subgroup of the highest‐quality studies, two reported significantly increased preterm birth (risk ratios (RR) from 2.4 to 4.0) following severe 2009 pandemic H1N1 (pH1N1) influenza illness, whereas those assessing mild‐to‐moderate pH1N1 or seasonal influenza found no association. Five studies of SGA birth showed no discernible patterns with respect to influenza disease severity (pooled odds ratio 1.24; 95% CI 0.96–1.59). Two fetal death studies were of sufficient quality and size to permit meaningful interpretation. Both reported an increased risk of fetal death following maternal pH1N1 disease (RR 1.9 for mild‐to‐moderate disease and 4.2 for severe disease).ConclusionsComparative studies of preterm birth, SGA birth and fetal death following maternal influenza disease are limited in number and quality. An association between severe pH1N1 disease and preterm birth and fetal death was reported by several studies; however, these limited data do not permit firm conclusions on the magnitude of any association.Tweetable abstractComparative studies are limited in quality but suggest severe pandemic H1N1 influenza increases preterm birth.

Optimal timing of influenza vaccine during pregnancy: A systematic review and meta‐analysis

“…The risks of hospitalisation and complications for respiratory illness during the influenza season are higher for pregnant women and increase by trimester . Furthermore, pregnant women infected with influenza might be more likely to have adverse birth outcomes …”

Progress and Remaining Gaps in Estimating the Global Disease Burden of Influenza

“…These efforts have led to recent publications from LMICs, supported by WHO, that provide important influenza disease burden data ( 34 ). WHO has also sponsored reviews of influenza-associated disease burden among pregnant women and their infants ( 35 , 36 ). Additional multinational collaborations are under way that will continue to develop more credible global influenza mortality and hospitalization estimates based on recent work to develop national estimates, as well as information on influenza burden among key high-risk groups (Figure) ( 6 ).…”

Maternal Influenza Immunization and Adverse Birth Outcomes: Using Data and Practice to Inform Theory and Research Design

“…Third, Hutcheon et al also concluded that the observed fetal benefits of maternal influenza immunization are biologically implausible, and they supported this claim with a forthcoming (unpublished) systematic review in which minimal support for a strong association between maternal influenza illness and adverse birth outcomes was found (9). We disagree; not only is biological plausibility among the least important of the classic Bradford Hill criteria for assessing causality (17), but the conclusion reached by Hutcheon et al ignores compelling empirical evidence to the contrary.…”

“…These differences might be particularly pronounced when comparing findings between geographic regions because climate, socioeconomic and nutritional status, and the baseline risk of adverse outcomes may all influence disease epidemiology. For their sample size calculations, Hutcheon et al used published estimates of influenza incidence and preterm birth rates (see Web Table 1 of their article), as well as measures of the association between maternal influenza illness and preterm birth calculated from previous observational studies (9). These estimates were derived almost entirely from studies conducted in temperate climates (predominantly the United States and Canada) with relatively short influenza seasons and low baseline rates of adverse birth outcomes.…”

“…There is in fact substantial evidence supporting the important role of infection and systemic inflammation in the causal pathway of preterm birth (18). Indeed, the authors of a recent systematic review of studies of the association between maternal influenza and birth outcomes (including several co-authors of the paper by Hutcheon et al) reported adjusted odds ratios for preterm birth of 2.4 and 4.0 in 2 studies of severe 2009 H1N1 influenza during pregnancy; these studies were deemed in that analysis to be of the “highest methodological quality” (9). Furthermore, the results of multiple well-designed studies, including publicly available data from recent RCTs, have been excluded from their analysis, ostensibly because they are implausible on purely hypothetical grounds.…”