Placental pathology, corticotropin-releasing hormone, timing of parturition, and fetal growth in the pregnancy outcomes and community health study

Background: Identification of vascular pathologies in delivered placentas and their associations with biomarkers measured during pregnancy may elucidate mechanisms of adverse pregnancy outcomes and inform early detection and intervention strategies. Objectives: To examine associations of placental vascular pathology with birth size and timing of parturition, and to evaluate maternal midpregnancy serum corticotropin-releasing hormone (CRH) levels as a marker of the above associations. Study design: The pregnancy outcomes and community health (POUCH) Study enrolled women at 16-27 weeks of pregnancy from five Michigan communities. Histological assessments of delivered placentas and assays of CRH in maternal blood sampled at enrollment were performed in a subcohort of 1152 participants. Five placental vascular pathology constructs were formulated: Maternal-Vascular-Obstructive (MVO), Fetal Vascular-Obstructive (FVO), Maternal Vascular-disturbance of Integrity (MVI), Fetal Vascular-disturbance of Integrity (FVI), and Maternal Vascular-Developmental (MVD). A four-level outcome variable combined small for gestational (SGA) yes/no and delivery timing preterm/term; the non-SGA/term served as the referent group. In multinomial logistic regression models, the five vascular pathology groups were evaluated in relation to the outcome variable and effect sizes were compared before versus after exclusion of participants with high CRH (top quartile). Results: Adjusted odds ratios (aOR) for MVO among SGA/term and SGA/preterm were 4.1 (95% CI: 2.2, 7.9) and 8.8 (95% CI: 3.3, 23.5) respectively. Among SGA/preterm births, the aOR was attenuated by similar to 40%, i.e. 5.4 (95% CI: 1.1, 26.2) after removing high CRH pregnancies. MVI and FVO were each associated with SGA/preterm, aOR = 3.7 (95% CI: 1.3, 10.3) and 10.5 (95% CI: 3.6, 30.8) respectively. Removal of high CRH pregnancies reduced the OR estimates by nearly half, i.e. MVI aOR = 1.9 (95% CI: 0.34, 10.9), FVO aOR = 6.0 (95% CI: 1.3, 28.6). MVI, FVI and MVD were each associated with greater odds of non-SGA/preterm, but the aORs showed little change after removing high CRH pregnancies. Conclusions: Obstructive placental vascular pathologies in maternal or fetal vessels are associated with SGA. High CRH levels coincided with a portion of pregnancies that share these complications, particularly among pregnancies that also ended prematurely.