Maternal Immune Activation During Pregnancy and Obstetric Outcomes: A Population-Based Cohort Study

Objective: Maternal immune activation has been proposed as a mechanism for adverse pregnancy outcomes, yet the mechanisms and effects of timing remain unclear. Immune disruption in early gestation may be particularly detrimental as this is an important period for placental development, which has been associated with the pathology of adverse obstetric outcomes. To increase our understanding of risk factors for adverse obstetric outcomes, we aim to investigate the association between multiple inflammatory and angiogenic markers during early pregnancy and adverse pregnancy outcomes in a large population-based cohort. Design: Prospective population-based pregnancy cohort study (n = 7513). Setting: Rotterdam, the Netherlands. Population: Pregnant women in Rotterdam between April 2002 and January 2006. Methods: Serum inflammatory markers (high-sensitivity (HS)-C-reactive protein (CRP), interleukin (IL)-1β, IL-6, IL-17a, IL-23, interferon (IFN)-γ) and angiogenic factors (sFlt-1 and PlGF) were analysed in repeated measures around 13–20 weeks gestation. A cytokine index was created using principal component analysis. Main Outcome Measures: Hypertensive disorders of pregnancy, spontaneous preterm birth and small for gestational age at birth. Results: HS-CRP, but not the cytokine index, was associated with increased risk of spontaneous preterm birth after multiple testing correction. We found no association of HS-CRP or the cytokine index with hypertensive disorders of pregnancy and small for gestational age at birth after multiple testing correction. Inflammatory and angiogenic factors were associated with each other, yet effect sizes were small. Conclusions: We found no strong evidence of a link between early gestation typical inflammatory marker levels and the risk of adverse pregnancy outcomes.