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

Abstract

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 ∼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.

KEYWORDS:

• Corticotropin-releasing hormone
• fetal growth
• maternal vascular complications
• placental pathology
• preterm birth

Acknowledgements

We would like to thank Dr. Qing Lu for review of the statistical methods; Drs. Joseph Marshall and Lynn Reuss for medical chart reviews; and Dr. Bertha Bullen for logistic oversight. We also thank the labor and delivery nurses for collection of placentas at the following participating hospitals: Borgess Medical Center, Bronson Methodist Hospital, Covenant HealthCare, Genesys Regional Medical Center, Hurley Medical Center, Ingham Regional Medical Center, McLaren Regional Medical Center, Sparrow Health System, and Spectrum Health.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability

For data requests, please Contact Dr Claudia Holzman at [email protected].

Additional information

Funding

This work was supported by the National Institute of Health (NIH) R01 HD34543); the March of Dimes Foundation [grants 20-FY01-38 and 20-FY04-37]; the Thrasher Research Foundation [Grant 02816-7]; and the Centers for Disease Control and Prevention [U01 DP000143-01]. Perng was supported by NIH/NICHD under T32-HD046377. The funders had no role in the design or conduct of research