ABSTRACT
Preeclampsia – an Evolving Story
Gus Dekker, University of Adelaide, Lyell McEwin Hospital
Although the exact aetiology and pathophysiology of preeclampsia remains unresolved, progress has been made over the last decades. Research during the 1970-1980s was dominated by 2 major findings; the exaggerated vascular response to exogenous vasoconstrictors (Gant), and the lack of proper physiological transformation of the spiral arteries by invading cytotrophoblast (Roberts and Pijnenborg). A disturbed PGI2/TXA2 balance was deemed to be the main mechanism causing the increased angiotensin-II sensitivity, this 1980s paradigm led to the first low-dose Aspirin studies. The lack of spiral artery transformation (wrongly) led to the idea that the ‘preeclamptic’ placenta was exposed to a pathologic degree of hypoxia – hypoxia considered to be THE culprit causing preeclampsia. The 1990’s introduced a new paradigm; the concept of preeclampsia being a systemic endothelial cell disease (Redman). Since then we have start to appreciate the complexity of endothelial ‘endocrinology’ with NO, EDHP, endothelin, microparticles etc, even prior to the discovery of angiogenic growth factors.
The real major breakthrough was the discovery of the pivotal role of pro- and anti-angiogenic factors (Karumanchi) – finally one of the main ‘toxins’, i.e. excess sFlt-1 was identified. The new insight in the pathophysiology went hand-in-hand with the realization that preeclampsia is a heterogeneous syndrome and clearly not a specific disease. Chris Redman was one of the first to introduce the concept of maternal versus placental preeclampsia, while research by Burton and Huppertz made it clear that the lack of spiral artery transformation (1) is more associated with IUGR than with preeclampsia per se, but also occurs in many cases of unexplained preterm labour, (2) and does not lead to hypoxia, but to a high velocity pulsatile blood flow in the spiral arteries, which is now deemed to be the main cause of damage to the vulnerable surface of the syncytiotrophoblast (STB).
Research over the last years has led to the concept of STB endoplasmatic reticulum (ER) stress with misfolding of proteins, (+) ER stress signals (e.g. sFlt-1 levels increasing), and (-) ER stress signals (e.g. PlGF levels decreasing). Preeclampsia is probably a kind of final common pathway reflecting STB stress caused by a variety of pathways; superficial transformation of the spiral arteries representing only one of these pathways, maternal obesity with the associated chronic inflammatory state representing another nowadays quite common pathway, while other studies clearly implicated infectious factors (e.g CMV) as potential stressors – all these pathways leading to the maternal syndrome that we know as preeclampsia. Preeclampsia in different regions of the world may have very different risk factors (causing problems with prediction), and also different common typical phenotypes. Exciting new trials are currently in progress (statins, PPI’s) to establish whether or not attempts to correct the pro-/anti-angiogenic imbalance will lead to improved perinatal and maternal outcome. Large epidemiologic studies have demonstrated that patients with a history of preeclampsia are at risk of chronic hypertension, type II diabetes, renal disease, and premature cardiovascular death. The time is ripe for systematic multi-disciplinary follow up studies for these women in order to establish whether or not lifestyle changes and/or targeted pharmacotherapy will lead to improved long-term outcome in these high-risk women. Comparison
of old vs new GDM Criteria: A retrospective analysis Aim:
To
identify whether the new ADIPS designed criteria have resulted in a difference
in outcomes in patients diagnosed with gestational diabetes mellitus (GDM) Methods:
Retrospective database review using both computer
database and case note review; 45 women were identified who met new but not old
diagnostic criteria for GDM, of whom 35 were suitable for further analysis
(group I). Their obstetric outcomes
(birthweight [BW], mode of delivery, onset of labour method, perineal damage
and neonatal admission to special care nursery [SCN]) were compared to 367
women diagnosed in 2014 (using old criteria only) (group II) and 70 BMI and
parity matched women without GDM identified through the South Australian
Pregnancy Outcome database (group III). Results: Patients in group II and III had comparable outcomes. Group I had an (almost significant) lower caesarean section (CS) rate than group II 28.6% vs 45.1% OR 0.49 (95% CI 0.23 - 1.04) and group III 40.0% OR 0.60 (95% CI 0.25-1.4). Group I had less macrosomia with BW > 4000g 5.7% vs 10.9% OR 0.59 (95% CI 0.12 – 2.20) vs 15.7% OR 0.32 (95% CI 0.07- 1.56). Group I had an increased induction rate compared to group III 59.4% vs 43.6% OR 1.89 (95% CI 0.79-4.57). Perineal damage and admission to SCN were consistent across all groups.
Conclusion:
The
results from this contemporary audit comparing patients with GDM only diagnosed
by the new ADIPS criteria with GDM patients as defined by the old criteria and
a non GDM control group demonstrate the absence of any detectable morbidity (at
least from an acute perinatal perspective) in the group of patients diagnosed
by the new but not the old GDM criteria. The trend to increase in IOL rate in
the only new GDM criteria group vs matched controls highlight the potential for
iatrogenic risks
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