A genetic variant in the placenta-derived MHC class I chain-related gene A increases the risk of preterm birth in a Chinese population
OBJECTIVE To evaluate evidence of placental haemorrhage (PH) obtained through maternal interviews, patient charts and placental pathology examinations as potential indicators of a 'bleeding pathway' to preterm delivery (PTD). DESIGN Prospective cohort. SETTING Fifty-two clinics in five communities in Michigan, USA (1998-2004). POPULATION A subset (n = 996) of cohort participants with complete placental pathology data. METHODS First-trimester bleeding and placental abruption were ascertained by mid-trimester interviews and chart review, respectively. Disc-impacting blood clot was defined as a gross placental examination finding of a blood clot impacting adjacent tissue. Microscopic haemorrhage was defined as 'high' (top quintile) scores on an aggregate measure of placental pathology findings suggestive of atypical maternal vessel haemorrhage. These four PH indicators were compared with one another and with risk of PTD assessed by logistic regression analyses. MAIN OUTCOME MEASURES Preterm delivery and PTD subtypes (i.e. <35 weeks, 35-36 weeks; spontaneous, medically indicated) compared with term deliveries. RESULTS Placental abruption cases had 2.3-fold to 5.5-fold increased odds of the other three PH indicators. Disc-impacting blood clots and microscopic haemorrhage were associated with one another (odds ratio [OR] = 4.6), but not with first-trimester bleeding. In a multivariable model that included all four PH indicators and confounders, risk of PTD < 35 weeks was elevated with first-trimester bleeding (OR = 1.9 [1.0, 3.4]), placental abruption (OR = 5.2 [1.7, 16.2]), disc-impacting blood clots (OR = 2.3 [1.0, 5.0]) and microscopic haemorrhage (OR = 2.4 [1.4, 4.2]). CONCLUSIONS Multiple clinical and subclinical PH indicators are associated with PTD, particularly early PTD.