The maternal immune response during pregnancy: Natural history during full-term pregnancy and association with preterm delivery.

摘要

Few studies have evaluated the influence of the maternal immune response early in pregnancy on preterm delivery. The goals of this study were to describe the natural history of serum Interleukin-1β (IL1β), Tumor Necrosis Factor-α (TNFα), Interleukin-6 (IL6) and Neopterin in women delivering at term and to examine the association between serum levels of IL1β, TNFα, IL6, Interleukin-10 (IL10) and Neopterin and preterm delivery. Data were obtained from a nested case-control sample of women from the population-based Odense Cohort study, Denmark, 1992–1994.; Women delivered at term had increasing levels of IL1β, TNFα, IL6 and Neopterin from early pregnancy to delivery, with further increase in Neopterin and IL6 at labor. Mean immune marker levels during term pregnancy were influenced by maternal age, gestational age, gravidity and levels of other markers and exhibited significant interindividual variation. Obstetric history influenced marker levels in term controls, but not in preterm cases who tended to have higher levels than controls regardless of obstetric history. Women with higher levels of IL10, Neopterin or TNFα, at enrollment had a significantly higher odds of preterm delivery even after adjustment for confounding, with odds ratios ranging from 2.3 to 4.7 respectively (highest category compared to lowest category). Overall, these markers, individually or in combination, exhibited moderate discriminatory ability and low predictive value for preterm delivery in all women at enrollment. When stratified by gravidity, the composite marker of high TNFα, (>50th percentile) and Neopterin (>75th percentile) was significantly associated with preterm delivery in primigravid women (OR = 23.62; PPV = 36.76%; NPV = 97.60%), but much less so in gravid women (OR = 1.65; PPV = 5.35%; NPV = 96.69%). Tree-structure algorithms identified similar predictive patterns for preterm delivery between primigravid and gravid women.; In conclusion, there is immune activation during pregnancy and significant interindividual variation in immune response. Individual marker levels are influenced by gestational age, maternal age, obstetric history and level of other immune markers. Preterm cases have significantly higher median levels of TNFα, IL10 and Neopterin early in gestation. These early markers are not strong predictors of preterm delivery in all pregnant women, but may be useful in sub-groups, e.g. primigravidae, for whom predictors are unidentified.