Socio-economic disparities in preterm birth: causal pathways and mechanisms

Preterm birth is the leading cause of infant mortality in industrialised so cieties. Its incidence is greatly increased among the socially disadvantage d, but the reasons for this excess are unclear and have been relatively une xplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involv es chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasin g hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use , and decidual vasculopathy. The second hypothesised pathway is a gene-envi ronment interaction based on a highly prevalent mutation in the gene for me thylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocy steinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested c ase-control study within a prospectively recruited and followed cohort of p regnant women with singleton pregnancies who deliver at one of four Montrea l hospitals that serve an ethnically and socio-economically diverse populat ion. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to as sess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA fo r the MTHFR mutation; and performs a digital and speculum examination to me asure cervical length and vaginal pH and to obtain swabs for bacterial vagi nosis and fetal fibronectin. After delivery, each case (delivery at < 37 co mpleted weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examin ation, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysi s of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with se quential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and pro cesses that mediate social disparities in preterm birth. This improved unde rstanding should help not only in developing strategies to reduce the dispa rities but also in suggesting preventive interventions applicable across th e entire socioeconomic spectrum.