THE CONTEXT
The passage describes maternal and placental risk factors, proposed disease mechanisms and several approaches to predicting pre-eclampsia.
Maternal and pregnancy-related risk factors
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Young or elderly primigravidas are listed in relation to first exposure to chorionic villi.
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Relevant family history includes hypertension, pre-eclampsia and diabetes.
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Obesity with a body mass index above 35 kg/m², insulin resistance, a history of PCOS and pre-existing vascular disease are listed as risk factors.
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New paternity and pregnancy following ART or IVF are also listed.
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Associated thrombophilias include antiphospholipid syndrome, protein C or protein S deficiency, and factor V Leiden.
Placental factors and proposed mechanisms
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Placental abnormalities include placental ischemia and hyperplacentosis. Hyperplacentosis involves excessive exposure to chorionic villi in molar pregnancy, multiple pregnancy or diabetes.
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Proposed mechanisms include failed trophoblast invasion with abnormal placentation, vascular endothelial activation by sFlt-1 and cytokine-mediated inflammatory responses.
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Other listed mechanisms include immunological maladaptation, coagulation abnormalities, increased oxygen-free radicals, an imbalance of angiogenic and antiangiogenic proteins, and trophoblast apoptosis.
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Polygenic predisposition and dietary deficiency or excess are also listed.
Combined screening at 11–13 weeks
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Multimarker screening combines maternal factors with mean arterial pressure, uterine artery pulsatility index, maternal serum pregnancy associated plasma protein-A and placental growth factor.
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These measurements are obtained at 11–13 weeks of gestation.
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The reported combined screening detected 77% of preterm pre-eclampsia cases occurring before 37 weeks and 38% of term cases, at a false-positive rate of 10%.
Doppler, renal and blood pressure predictors
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A uterine artery diastolic notch at 24 weeks can predict possible fetal growth restriction, but the passage specifically states that it does not predict pre-eclampsia.
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Raised serum uric acid and the appearance of microalbuminuria are described as predictors of pre-eclampsia.
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An average mean arterial pressure above 90 mm Hg in the second trimester may predict disease onset.
Biomarkers and investigational approaches
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The insulin resistance marker list includes increased leptin, TNFα and homocysteine, with decreased placental growth factor, SHBG and pregnancy associated plasma protein-A.
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A separate statement reports increased maternal serum sFlt-1 and pregnancy associated plasma protein-A in women with pre-eclampsia.
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Detection of free fetal DNA in maternal plasma during early pregnancy may be predictive of pre-eclampsia.
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Proteomic, metabolomic and transcriptomic markers are being studied.
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The passage cautions that the prediction tests discussed have not provided convincing evidence of clinical usefulness.