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Introduction
Preeclampsia (PE) is a common and life-threatening hypertensive disorder of pregnancy. Diagnosed clinically by elevation in maternal blood pressure after 20 wk gestation, it is often accompanied by proteinuria. The biological onset is insidious, due to the subtlety of the symptoms (ACOG 2002). Typically seen in women having their first pregnancy, PE can rapidly progress to eclampsia, with seizures and risk of maternal and/or fetal death. Once PE is diagnosed, medically indicated delivery is considered because such an intervention is generally curative for the mother. However, if PE is diagnosed prior to 34 wk gestation, the risks involved in delivering a very immature baby must be weighed against the risks for both mother and baby that are imposed by continuing the pregnancy.
The pathophysiology of PE is not fully understood and it is unclear whether one should look for causative conditions in early pregnancy or later, when the syndrome becomes clinically apparent (Levine et al. 2005; Thadhani et al. 2004). Although the majority of cases are diagnosed late in the third trimester, evidence suggests that in some instances an underlying placental abnormality was present much earlier in gestation, as inferred from evidence of shallow invasion of the myometrium and inadequate remodeling of spiral arteries (Powe et al. 2011). At a later stage in gestation, inadequate perfusion of the placenta may cause an increase in maternal blood pressure, at which point the condition becomes clinically apparent. For cases where placental abnormalities originate early in gestation (Powe et al. 2011), the critical period for causative exposures (and preventive measures) may be during the first trimester (Huppertz 2008), despite the fact that the condition will not be diagnosed until much later.
Based on epidemiologic research, high maternal body mass index (BMI) (Thadhani et al. 1999), polycystic ovary syndrome (Palomba et al. 2015), preexisting hypertension, primiparity (Hernández-Díaz et al. 2009), family history (Boyd et al. 2013; Esplin et al. 2001; Skjærven et al. 2005), and a history of PE (Boyd et al. 2013) are recognized risk factors. There is also evidence that risk is associated with short stature (Basso et al. 2004), high altitude (Dávila et al. 2012), subfecundity (Basso et al. 2003), and long inter-pregnancy interval (Basso et al. 2001; Skjærven et al. 2002). Maternal cigarette smoking,...