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Key Terms

  1. Diastolic notch: well seen depression or indentation in the initial early diastolic component of the Doppler waveform that indicates increased resistance to blood flow in the vascular territory being studied.

  2. ART: assisted reproductive technology.

  3. PAPP-A: plasma-associated protein-A is a protease secreted by the placenta. Low levels are associated with increased risk of trisomy 21 as well pregnancy-related complications such as miscarriage, preg nancy-induced hypertension, fetal growth restriction and gestational diabetes.

  4. PlGF: placental growth factor is a protein of the vascular endothelial growth factor subfamily involved in angiogenesis. It is highly expressed in the placenta at all stages of gestation. Low levels of PlGF are associated with an increased risk for preeclampsia.


Preeclampsia is a gestation-specific syndrome that affects 2% to 8% of all pregnancies.1 It is characterized by new onset hypertension and proteinuria beginning at or after 20 weeks’ gestation.2 The incidence among nulliparous women is not only higher but has also increased in the United States, from approximately 12% to 28% over a period of 17 years.3,4 Possible reasons for this increase include a trend toward higher BMI and maternal age at the time of conception and a higher number of pregnancies conceived using assisted reproductive technology (ART).5 Despite tremendous progress in obstetrical care during the 20th and early 21st centuries, preeclampsia and eclampsia continue to claim maternal and fetal lives and contribute significantly to neonatal morbidity and mortality.6-8 This is largely due to a lack of effective strategies to prevent and treat the disease. The only known cure is to remove the placenta, which implies early delivery and prematurity in a substantial proportion of cases.2

The etiology of preeclampsia is multifactorial. However, impaired placentation is considered to play a key role in the development of the disease, particularly early onset preeclampsia, ie, preeclampsia requiring delivery before 34 weeks.2 It is not clear whether late onset preeclampsia has a different pathogenic mechanism or represents a different form of the same disease.2,9 Although late onset preeclampsia represents the majority of the cases (approximately 78%-88%),10,11 early onset preeclampsia is associated with a high frequency of histologic placental lesions consistent with maternal underperfusion12 and a significantly higher risk of perinatal complications (ie, small-for-gestational age [SGA] status, fetal and neonatal death, and combined perinatal death and morbidity).11

Low-dose aspirin has been proposed as a prophylactic agent to prevent preeclampsia related to impaired placentation. A meta-analysis of 31 trials showed that the administration of low-dose aspirin to high-risk patients is associated with a reduction of approximately 10% in the rate of preeclampsia (relative risk [RR] = 0.90, 95% confidence interval [CI] = 0.84-0.97).13 A meta-analysis published in 2010, with analysis stratified according to the gestational age at which low-dose aspirin prophylaxis was initiated, showed a 50% reduction in the prevalence of preeclampsia when prophylaxis started ...

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