Potential pathways by which maternal second-hand smoke exposure during pregnancy causes full-term low birth weight

Low birth weight (LBW, birth weight <2500 g) may result from preterm birth or intrauterine growth restriction (IUGR), which can occur simultaneously in pregnancy1. There is accumulating evidence that LBW is not only the strongest single risk factor for perinatal, neonatal and infant mortality2, but is also related to neurological and behavioural problems in childhood3,4 and chronic diseases in adulthood5,6. Therefore, researchers have started paying attention to studies on the etiological factors associated with LBW and the potential pathophysiological mechanisms. It is well documented that maternal exposure to second-hand smoke (SHS) is an important risk factor for LBW. A recent meta-analysis estimated that maternal exposure to SHS during pregnancy reduces mean birth weight by 31–60 grams and may increase the risk of LBW by 1.16–1.60 times7. However, the biological mechanisms by which maternal exposure to SHS during pregnancy causes LBW have not been established. A potential pathway may be that maternal exposure to SHS during pregnancy causes maternal inflammation, which disrupts the placenta’s ability to transfer sufficient nutrients and oxygen to the foetus, and finally results in LBW. The aforementioned hypothesis is suggested by the following strands of evidence. First, SHS exposure leads to abnormal levels of inflammatory markers in different populations8,9. Second, the elevated maternal inflammatory markers are independently related to LBW10 and mediate the associations between periodontal disease11, maternal sleep disturbances during pregnancy12, maternal pre-pregnancy body mass index (BMI)13 and LBW. Third, the placenta is associated with birth weight and IUGR14,15,16. Fourth, maternal smoking during pregnancy impairs the structure and functioning of the placenta17. Fifth, placental weight partially mediates the effects of prenatal factors such as pre-pregnancy obesity, gestational diabetes mellitus and excessive gestational weight gain on foetal growth18. Sixth, abnormal inflammatory markers have been found in the placentas of LBW cases19. To the best of our knowledge, there is no research that links the above evidence together to explore the plausible mechanisms. As such, this study aimed to explore the potential pathways that integrate maternal inflammation and the placenta, which might explain the mechanism by which maternal exposure to SHS during pregnancy leads to LBW.