Herpes simplex virus type-2 infection in pregnancy: no risk of fetal death: results from a nested case–control study within 35,940 women

The aim of this study was to assess the association of fetal death with herpes simplex virus type-2 (HSV-2) antibody status during pregnancy: 1. presence of antibodies in first trimester; 2. appearance of antibodies (incident infection); 3. increase in antibody titre; and 4. loss of antibodies. Prospective study. The source population was a cohort of 35,940 pregnant women in Norway. Nested case–control study within the cohort. Cases were all women in the study population who experienced a fetal death after the 16th weeks of gestation ( n = 281), and controls were 961 randomly selected women with a live born child. HSV-2 antibody status. Twenty-nine percent (82/281) of women with a fetal death and 27% (256/961) of the controls had of HSV-2 antibodies present in the first trimester (odds ratio 1.1, 95% CI 0.8–1.5). HSV-2 antibodies appeared in 2% (3/136) of initially seronegative cases and 3% (16/623) of the controls during pregnancy (odds ratio 0.9, 95% CI 0.2–3.0). An increase in HSV-2 antibodies occurred in 4% (2/55) of initially seropositive cases and 7% (16/231) of the controls (odds ratio 0.5, 95% CI 0.1–2.3). Loss of HSV-2 antibodies in initially seropositive women was not associated with fetal death, 42% (23/55) of the cases and 45% (104/231) of the controls seroreverted (odds ratio 0.8, 95% CI 0.5–1.6). Differences in follow up time, age and parity were controlled and did not influence the comparisons between cases and controls. This study provides no evidence of an association between HSV-2 infection during pregnancy and fetal death.