Abstract

Small for gestational age (SGA) neonates face several complications in the immediate neonatal period as well as long-term impairment in psychomotor and developmental outcomes. Fetal growth restriction is shown to have multiple etiologies, however the relationship between inflammatory dysregulation in pregnancy and birth weight remains incompletely understood. Our objective for this study was to evaluate a central link between systemic maternal inflammation and birth weight. This was a secondary analysis of a longitudinal multicenter study of women with singleton gestations. Maternal serum and cervico-vaginal fluid (CVF) specimens were collected in all trimesters. Cytokines (IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, CRP) were measured using a multiplex beadlyte assay on a luminex IS-100. SGA (defined as birth weight less than 10th percentile for gestational age) was determined using the Fenton Growth Chart. Repeated measures analysis was used to evaluate differences in cytokine profiles by SGA infant status, adjusting for maternal age and first trimester smoking status. Cytokine values were log-transformed prior to all data analyses. Statistical analyses were performed using SAS 9.4 with an alpha level of 0.05 throughout. Pregnant women (n= 317) underwent screening in each trimester. The rate of SGA infants among the study subjects was 7% (n=23). Serum cytokine data was available for 240, 227 and 214 subjects in the first, second and third trimesters, respectively; CVF data was available for 226, 210 and 187 subjects, respectively. In the bivariate analysis, first trimester serum IL-10 was significantly higher in women with SGA infants (p=0.044), while first trimester CVF IL-10 was lower in patients with SGA infants, trending towards significance (p=0.063). In the adjusted analysis, serum IL-1β levels were significantly higher (p=0.043) and serum CRP levels were significantly lower (p=0.036) among women who delivered SGA infants versus those who delivered infants of normal weight, regardless of trimester. Our results indicate that altered levels of inflammatory cytokines over the pregnancy time course may be associated with small for gestational age neonates. Further research is warranted to understand the immunomodulatory mechanisms involved in affecting fetal growth.

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