Maternal circulating immune factors and fetal growth : c-reactive protein, tumor necrosis factor - α, interleukin - 6, in mid-pregnancy and birthweight for gestational age

Inflammation pathways may contribute to fetal growth restriction. Observations of immune molecules such as the acute phase reactant, C-reactive protein (CRP) and fetal growth have produced mixed results, therefore further investigation is warranted. We analyzed data from 1,308 sub-cohort women enrolled at 16 -27 weeks completed gestation in the Pregnancy Outcomes and Community Health (POUCH) Study from 52 prenatal clinics in 5 Michigan communities. Using a US population reference of birthweights for gestational age, POUCH infants were grouped as small for gestational age (SGA) (≤10th percentile), large for gestational age (LGA) (≥ 90th percentile), or appropriate for gestational age (AGA). Levels of inflammatory signaling molecules Tumor Necrosis Factor -  (TNF-), Interleukin – 6 (IL-6), and CRP were measured in maternal blood collected at enrollment and compared across groups who delivered either SGA, LGA, or AGA infants. Maternal TNF- α and IL-6 levels did not differ across the three groups. Unadjusted Mean CRP level of the SGA, 3.76 μg/L, was significantly lower than that of the AGA (5.43 μg/L, p=0.002) or LGA (6.36 μg/L) in linear regression models. Following adjustment for maternal age, race/ethnicity, pre-pregnancy BMI, gestational age at enrollment, Mean CRP values were 3.89 μg/L for SGA 5.41 μg/L for LGA 5.1, and μg/L for AGA (p=0.008 for SGA vs AGA). In sensitivity analyses, differences remained after excluding women with a pre-pregnancy BMI <18.5, hypertensive disorders of pregnancy, extreme CRP values, or antibiotic prescription < 2 weeks before blood draw. Further analysis should assess characteristics of the maternal-fetal interface for clues to relationships between maternal inflammatory status at 16 – 27 weeks gestation and birthweight outcomes.