Natality decline and miscarriages associated with the 1918 influenza pandemic: the Scandinavian and United States experiences

Pregnancy has been identified as a risk factor for severe illness and death during all the influenza pandemics of the 20th century and in the 2009–2010 influenza A(H1N1) pandemic. In the 1957 influenza pandemic, ∼50% of the deaths in women of childbearing age occurred in pregnant women and resulted from primary viral pneumonia following influenza infection [1–3]. Similarly, although pregnant women comprise ∼1% of the US population today, they accounted for 5% of influenza-related deaths during the 2009 pandemic; furthermore, pregnant women were at elevated risk for admission to intensive care units and preterm delivery [4–6]. In contrast to the risk of maternal illness during pregnancy, the impact of influenza on the fetus and likelihood of miscarriage has been less studied [7]. Although studies have shown that maternal influenza vaccination improves fetal and infant outcomes [8, 9], little is known about whether maternal influenza infection has the potential to terminate pregnancies, and comprehensive data are lacking on the association between influenza and birth outcomes. This issue could have important implications for public health strategies and clinical care for pandemics as well as seasonal epidemics. Investigating the impact of influenza on pregnancy is a challenge, because miscarriages may not be directly linked to influenza when patients are referred to clinics, especially if miscarriage occurs several weeks after primary viral infection. In addition, early pregnancy loss may occur unbeknownst to women who have not yet discovered that they are pregnant. Clinical reports from the 1918 pandemic period support a link between influenza and elevated maternal morbidity, mortality, pregnancy loss, and preterm labor [10–12]. In a 1919 report of 1350 pregnant women with influenza, 26% of case subjects miscarried (the largest proportion in the first trimester), whereas 52% of pneumonia-complicated case subjects miscarried [13]. This phenomenon associated with the 1918 pandemic appears to have been geographically widespread; a preponderance of miscarriages following pandemic peak activity was described in the Philippines [14], and an increase in miscarriages in women 5–9 months pregnant followed by a baby boom was reported in Norway [15]. In more recent literature, a possible association was noted between seasonal influenza A(H3N2) and a cluster of miscarriages [16]. Small observational studies of pregnant women infected with the 2009 pandemic influenza A(H1N1) virus reported preterm deliveries and fetal deaths [17, 18]. Despite these geographically limited reports and case series, the association between maternal influenza and pregnancy loss has not been quantified. In this study, we utilized historical epidemiological records from the 1918 influenza pandemic in 3 Scandinavian countries and the United States to examine the relationship between influenza and pregnancy outcomes at the population level. We hypothesized that if influenza infection in pregnant women can cause miscarriages on a large scale, then a decline in births would occur within 9 months of the peak pandemic activity. Data from contemporaneous national surveillance systems were acquired from library archives to elucidate the potential temporal associations between influenza activity and birth patterns, and to quantify the risk of miscarriage associated with influenza infection.