Mediating effect of oxidative stress on association between nicotine and unexplained recurrent spontaneous abortion

[Background] Previous studies have confirmed that nicotine exposure is an independent risk factor for miscarriage, but it is not clear whether nicotine causes unexplained recurrent spontaneous abortion (URSA) through oxidative stress. [Objective] To explore potential mediating effect of oxidative stress on the relationship between nicotine exposure and URSA. [Methods] Using a 1∶1 matched case-control study, 88 patients with URSA visiting Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University from April to October in 2018 were selected as the case group, and 88 pregnant women without adverse pregnancy outcomes and seeking induced abortion in the outpatient clinic of the same hospital were selected as the control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in urine were determined by enzyme-linked immunosorbent assay, and the level of urinary nicotine was determined by gas chromatography-mass spectrometry. Conditional logistic regression was used to analyze the associations of nicotine, 8-OHdG, and 8-iso-PGF2α with the risk of URSA. Multiple linear regression was used to analyze the association of nicotine with 8-OHdG and 8-iso-PGF2α. The potential mediating effect of oxidative stress on URSA after nicotine exposure was explored by dichotomous mediating model. [Results] The median concentrations (creatinine corrected) of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were 7.78, 4.84, and 44.10 μg·g−1, respectively, while those of the control group were 6.48, 3.34, and 29.39 μg·g−1, respectively. The concentrations of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were all higher than those of the control group (P < 0.05). The results of conditional logistic regression model showed that after adjusting selected confounding factors, compared with the Q 1 groups of nicotine and 8-iso-PGF2α, the OR (95%CI) values of URSA in the Q4 groups were 4.20 (1.33-13.29) and 6.25 (1.66-23.59), respectively. Compared with the Q1 group of 8-OHdG, the OR (95%CI) values of URSA in the Q1, Q2, and Q3 groups were 5.47 (1.43-20.93), 4.24 (1.28-14.07), and 6.36 (1.82-22.28), respectively. The results of multiple linear regression showed that after adjusting confounding factors, there was a positive correlation between urinary nicotine and 8-OHdG in both the case group and the control group, and the b (95%CI) values were 0.76 (0.67-0.86) and 0.81 (0.67-0.95) respectively