Among low-risk pregnant patients, sFlt1 has been reported to be significantly elevated by 33 to 36 weeks' gestation and >5 weeks before the clinical onset of preeclampsia [10]. Similarly, maternal concentrations of sEng are significantly elevated at 25 to 28 weeks' gestation and 9 to 11 weeks before clinical onset of preterm preeclampsia, and 33 to 36 weeks' gestation and 9 to 11 weeks before the clinical onset of term preeclampsia [9]. Maternal concentrations of PlGF are also reported to be significantly lower by 13 to 20 weeks' gestation among women who later develop preeclampsia compared with similar low-risk control subjects [10]. In contrast to low-risk subjects, there has been limited investigation of the differences in these angiogenic factors across pregnancy among high-risk subjects. Moore Simas et al. evaluated the predictive value of maternal sFlt1 and PlGF between 22 and 36 weeks' gestation in a combination of several high-risk populations including patients with chronic hypertension and pre-gestational diabetes [14]. This study reported that mean serum sFlt1 and sFlt1/PlGF ratio were higher at 22 weeks' gestation in subjects who developed early onset preeclampsia (<34 weeks) compared with uncomplicated controls, and that serum sFlt1 was significantly higher after 31 weeks' gestation in subjects with late onset preeclampsia (>34 weeks). The authors conclude that these angiogenic factors may be predictive of preeclampsia in high-risk populations. However, this study is limited by a small sample size, with 12 preeclamptic subjects total, 5 with early onset and 7 with late onset preeclampsia; as well as a significantly mixed population of high-risk groups (all 5 early onset preeclamptic subjects had chronic hypertension, 2 with pre-gestational diabetes, 1 with renal disease, and 2 with previous preeclampsia) making it difficult to conclude the significance of these factors within any single high-risk group. A study by the same group also reported that maternal serum sFlt1 and PlGF are significantly elevated in subjects with multifetal gestations as early as 22 weeks' gestation [15]. These data are similar to the data reported in this study, as well as our finding that sEng is also significantly higher in all pregnant women with multifetal gestations. The explanation for the elevated angiogenic factors in women with multifetal gestations is likely related to the increased placental mass, however we lack sufficient information to provide a complete explanation. This same explanation was also proposed by Maynard et al. as well as reporting a significant correlation between circulating sFlt1 and placental mass in multifetal gestations (r = 0.62, p = 0.0002) [15]. In addition, a recent study by Sibai et al. investigated the predictive value of maternal sFlt1 and PlGF between 12 to 19 weeks and 24 to 28 weeks' gestation among 704 patients with previous preeclampsia and/or chronic hypertension (14.7% had both conditions) [16]. The authors reported that PlGF concentrations were significantly lower at baseline and sFlt1 concentrations were higher at 24 to 28 weeks' gestation in subjects who later developed preeclampsia, and these differences were most noticeable among subjects who developed preeclampsia before 27 weeks' gestation. However, overall these differences were modest, and the sensitivities and positive predictive values were low suggesting that the clinical utility of these markers is limited.