752 - Effects of Maternal BMI and Systemic Inflammation on Progesterone Levels during Pregnancy

Despite many improvements in perinatal medical care preterm birth represents 10% of all live births and contributes to 1/3 of infant mortality. Two prominent mechanistic theories have been separately associated with preterm birth: deficiency of progesterone (P4) or activation of inflammation. The role of sub-clinical inflammation caused by obesity during pregnancy on progesterone progression has not be defined.

Objective: To test the hypothesis that maternal BMI is associated with systemic inflammation and leads to low P4 during pregnancy. 

Design/Methods: A cohort of 209 pregnant women were recruited at first trimester during their first visit at Maternal-Fetal Medicine department, University of Kentucky HealthCare. Maternal demographics, BMI, and blood samples were collected at recruitment (FTS, average GA 12.5wks) and at a follow-up visit (Growth, average GA 28.9wks). Umbilical cord blood was also collected at delivery. Plasma c-reactive protein (CRP) was measured with ELISA. Serum P4 levels were measured at a certified clinical laboratory. Maternal and neonatal outcomes were extracted from electronic medical record. Correlations among BMI, CRP and P4 were analyzed with Prizm GraphPad.  

Results:

Maternal P4 levels elevated during pregnancy progression as expected, with an observation of high P4 in cord blood. Net increase of P4 between early third trimester (Growth) and first trimester (FTS) positively correlated with fetal weight at Growth (Pearson r=0.24, p=0.005) and weight percentile at birth (Pearson r=0.23, p=0.009). Maternal BMI (FTS-BMI) highly correlated with P4 at both 1^st and 3^rd trimester in a negative way (Pearson r=-0.43, p< 0.001 and r=-0.25, p=0.002, respectively), but not associated with cord blood P4. Elevated CRP has been observed in pregnancy women, even in normal weight cases; whereas cord blood had normal levels. Maternal FTS-BMI highly correlated with CRP (Pearson r=0.50 and 0.54 for 1^st and 3^rd trimester respectively, p< 0.001). FTS-CRP negatively correlated with 1^st trimester P4 (Pearson r=-0.43, p< 0.001) and 3^rd trimester (Pearson r=-0.18, p=0.04), but not cord blood P4.

Conclusion(s):

Our study observed that BMI is associated with elevated systemic inflammation and decreased maternal serum progesterone levels. An inflammation marker (CRP) directly correlated with progesterone level negatively, in both the maternal and fetal circulations. Adverse pregnancy and neonatal outcomes may be related to a deficiency in progesterone to mitigate pathophysiologies mitigated by inflammation in either the mother and the newborn.