Maternal Influenza-Like Illness and Neonatal Health During the 1918 Influenza Pandemic in a Swiss City

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. Using 2177 historical birth records from University Maternity Hospital of Lausanne, it was estimated 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 the trimester of ILI during pregnancy or on fetal sex. Generalized linear models and robust linear models were used to analyze the association between ILI and gestational age, stillbirth, and anthropometric measurements, adjusting on covariates. Analyses were stratified by fetal sex. A total of 282 (13%) women developed ILI during pregnancy. Exposure to ILI was associated with lower anthropometric measurements: low birthweight (LBW; <2500 g) (marginally adjusted percentage was 13.3% compared with 6.9% in the unexposed group; difference, 6.4 percentage points [95% CI, 5.5 to 7.2 percentage points]). There was strong evidence that third trimester exposure was associated with worse adverse pregnancy outcomes, including with LBW (difference, 12.8 percentage points [CI, 11.8 to 13.7 percentage points]) and preterm birth rates (difference, 9.4 percentage points [CI, 8.2 to 10.6 percentage points]). Maternal ILI may have triggered premature birth. The magnitude of the declines in anthropometric parameters was higher among male fetuses, and they had a higher stillbirth rate. For instance, males exposed during the third trimester had their birthweight lowered by 228.4 g (CI, -391.0 to -65.8 g) compared with 126.3 g among females [CI, -256.6 to 4.0 g]. Only 41% of infants exposed to first-trimester ILI were males, suggesting a selection against male fetuses through miscarriage. Our findings may not generalize to the entire population of Lausanne, as 34% of births were home births at the time.