Pre-eclampsia (PE) is a multisystem disorder that affects around 5 % of pregnancies, and is a leading contributor to obstetric morbidity [[1], [2], [3]]. There remains no definitive treatment except for delivery of the baby and placenta, which is often necessitated preterm, due to declining maternal and/or fetal wellbeing.

There is increasing evidence implicating complement dysregulation in the pathogenesis of PE. Animal models demonstrate placental complement activation inducing defective angiogenesis, abnormal placentation, and fetal demise [[4], [5], [6]], with complement inhibition rescuing pregnancy [[4], [5]]. Studies of human placental tissue from women with PE report excess C4d deposition compared to healthy pregnant controls, associated with preterm birth [7] and fetal growth restriction [8]. C3d and C5b-9 deposition may also be increased in PE [[9], [10], [11], [12]], but other studies refute this [13]. Studies of maternal plasma drawn in early pregnancy report increased Bb concentrations in women who later developed PE [[14], [15]], suggesting excessive alternative complement pathway activity during early placental development. Raised concentrations of C5b-9 in PE demonstrate terminal pathway activation [[16], [17], [18]] and may be associated with PE severity [19]. Data on umbilical cord blood (UCB) complement is extremely limited. UCB C5a appears to be raised in PE [20], suggesting that complement activation affects the fetal compartment, although data on UCB Bb are conflicting [[21], [22]].

Complement-modifying agents are undergoing rapid development and may provide novel opportunities to treat complement-mediated diseases [[23], [24], [25], [26], [27]]. Despite the growing body of evidence, it remains unclear whether raised concentrations of circulating complement reflect a general heightened inflammatory state in PE or are directly associated with placental complement-mediated injury. We therefore aimed, for the first time, to simultaneously compare markers of local placental complement deposition with systemic complement activation in the maternal and fetal circulation between PE and healthy pregnancy. The results will potentially provide further support for the role of complement activation in the pathogenesis of PE, and may also provide insight into the sequence of events leading to complement activation on a local and systemic level.