Background: Several studies have linked coffee intake and smoking to foetal death, but a possible interaction between both exposures remains unknown.
Methods: We studied, within the Danish National Birth Cohort, the potential interaction between smoking and coffee drinking while pregnant on the risk of foetal (early and late) death. The study included 90 086 pregnant women, with information about their smoking habit and coffee intake in early pregnancy, and several potential confounding factors. Interaction was studied by calculating both the hazard ratio (HR) in Cox's regression (linear and smoothed restricted cubic spline) and the interaction contrast ratio (ICR).
Results: Women who neither smoked nor drank coffee were used as the reference group. Drinking more than 3 cups/d of coffee was associated with the highest risk of foetal death, spontaneous abortion and stillbirth for all smoking status (non-smoker, ≤10 or > 10 cigarettes/d). Among smokers, the combination with drinking <3 cups/d of coffee presented the lowest HRa for foetal death, spontaneous abortion and stillbirth. The ICRs were negative when considering smokers who had a coffee intake up to 3 cups/d, but they were positive for those who had a higher coffee intake, suggesting the effect of coffee intake may be non-linear.
Conclusion: Our results suggest that the combined effect of smoking and coffee intake during pregnancy on the risk of foetal death is coffee-dose-dependent. A low coffee intake may reduce the risk of foetal death associated with smoking while a high coffee intake increases the risk.