We thank Jadli and co-authors for their interest in our short review and agree with much of what they say. Of course there is the need for robust biomarkers for preeclampsia, whether the disease is early or late onset, as both have important short- and long-term adverse effects on mother and child. Their conclusion that more research is needed is incontrovertible.

Jadli et al remain wedded to the model of poor placentation as the key pathology for preeclampsia. However, we give evidence that the pathology involves more than spiral artery remodeling namely syncytiotrophoblast stress, which we show is relevant not only to early- but also to late-onset disease, the latter not being associated with poor placentation. As late-onset preeclampsia is commoner than the early-onset form it is important that we understand its origins.

We present the evidence that at term, the syncytiotrophoblast becomes stressed when placental growth reaches and exceeds the capacity of the uteroplacental system. This accounts for the increasing placental hypoxia that has been documented at this time . The short-term duration of this pathology explains why fetal growth restriction is not a prominent feature and why the classic biomarkers are poorly predictive, indeed not even efficiently diagnostic (of late-onset disease). At this stage the distinction between cases and controls is blurred since term controls are not truly normal (what we call pseudonormal). In consequence the biomarkers reflect syncytiotrophoblast stress in an increasing proportion of term and postterm pregnancies of which many are still free of signs of preeclampsia.

We specifically state that spiral artery remodeling is not an all-or-none event, but on a spectrum. However, even complete remodeling imposes a limit on intrauterine placental maintenance, which eventually can lead to syncytiotrophoblast stress.

We do not agree with the authors’ statement “that vascular mimicry involved in remodeling of uterine arteries gets completed in pregnancy at term.” As pregnancy progresses, endovascular trophoblast disappears, leaving the remodeled spiral arteries to be reendothelialized. Subintimal cushions remain as scars of the tissue damage intrinsic to remodeling, which appears to be largely completed in the first half of pregnancy.