Background: Exposure to the 1918 influenza pandemic may have been associated with preterm birth (<37 weeks). Other outcomes, such as infant size or weight, have rarely been explored. Objective: To estimate whether in utero exposure to maternal influenza-like illness (ILI) during the 1918 pandemic was associated with pregnancy outcomes, and whether associations varied depending on ILI timing or on fetal sex. Design: Cross-sectional study using historical birth records. Setting: Lausanne maternity hospital. Participants: 2,177 singletons born during the pandemic. Measurements: The impact of ILI on gestational age, stillbirth, and anthropometric measurements, adjusted on covariates in generalized linear models. Analyses were stratified by fetal sex. Results: 282 women developed ILI during pregnancy. ILI exposure was associated with lower anthropometric measurements: the odds ratio (OR) of low birth weight (<2,500g) was 2.06 [95%CI 1.33; 3.20]. In multivariable models, there was strong evidence that third trimester exposure was associated with adverse pregnancy outcomes, including with a higher preterm birth rate (OR 2.87 [95%CI 1.53; 5.39]). There was moderate evidence that first-trimester ILI exposure was associated with lower anthropometric measurements, in univariable models only. The magnitude of the declines in anthropometrics parameters was higher among male fetuses, and they had a higher stillbirth risk. Only 41% of infants exposed to first-trimester ILI were males. Limitation: our findings may not generalize to the entire population of Lausanne, as 34% of births were homebirths at the time. Conclusion: maternal ILI may have triggered premature birth. The low sex ratio at birth for first-trimester exposure may indicate selection against males through miscarriage, but males were still more vulnerable than females to third trimester exposure. Primary funding source: Swiss National Science Foundation.

The authors have declared no competing interest.

The authors thank the Swiss National Science Foundation (SNSF, project number 197305, Grantee Kaspar Staub) for providing financial support.

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Ethics committee of Canton of Zurich gave ethical approval for this work.

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The data that support the findings of this study and the codes used for the data analysis will be made publicly available in the following online repository, after publication of the paper.

https://github.com/MathildeLV/Lausanne_influenza