The median age of the women was 32.9 (standard deviation [SD] +/− 5.4) years and median body mass index at the first prenatal visit was 25.9 (SD +/− 6.0) kg/m2. The study population was largely self-identified as Caucasian (n=129) or Hispanic (n=34). Other racial/ethnic groups included Asian (n=6), African-American (n=5), and unknown (n=8). The median length of gestation was 39.7 (SD +/−1.8) weeks (range 26–42.1) and the median birth weight was 3495 g (SD +/−542; range 851–4767). The gender of the offspring was 54% male and 46% female.
Medians (and ranges) of the angiogenic factors measured in the first and second trimesters, and the change in the measurements from first to second trimester are reported in . All angiogenic measures show substantial between-person variation. As expected, PlGF concentrations increased dramatically from first to second trimester, while median sFlt1 and sEng decreased slightly. The increased PlGF and decrease or constant sFlt1 and sEng levels between first and second trimester of pregnancy have been shown in other populations [4
], including in a different subgroup of the control population of the MOMS cohort [8
]. The increase in PlGF from first to second trimester resulted in much lower anti-angiogenic ratios of sFlt1/PlGF and (sFlt1+sEng)/PlGF in the second trimester compared with the first trimester.
Angiogenic Protein Concentrations and Ratios in the First and Second Trimester and Change between Trimesters.
The adjusted associations of maternal characteristics with the angiogenic proteins and ratios measured in the first trimester are presented in . Maternal age in tertiles demonstrated a nonlinear association with higher PlGF concentrations associated with women in the middle tertile of age 31–34.5 years of age (=0.03). Although of borderline significance, nulliparous women had higher first trimester sFlt1 concentrations than parous women (P=0.06) resulting in a higher anti-angiogenic sFlt1/PlGF ratio (P=0.05). sEng levels were inversely associated with increasing BMI (P=0.002) while sFlt1 and sFlt1/PlGF ratio increased with greater BMI (P=0.004 and P=0.007, respectively).
Adjusted Mean First Trimester Angiogenic Protein Concentrations by Maternal Characteristicsa.
The associations of the maternal characteristics with second trimester angiogenic factors were largely similar to those found in the first trimester () except for maternal age, which no longer demonstrated an association with PlGF. Nulliparous women had higher sFlt1 levels (P=0.001) and consequently a higher mean sFlt1/PlGF ratio (P=0.003) in the second trimester when compared to parous women. BMI was again inversely associated with sEng (P=0.0009) and positively associated with sFlt1 levels (P=0.008). The anti-angiogenic ratio of sFlt1/PlGF also increased with BMI (P=0.02).
Adjusted Mean Second Trimester Angiogenic Protein Concentrations by Maternal Characteristicsa.
Systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP) were measured at both the first and second trimester visits when samples were collected to measure angiogenic factors. The correlations of SBP, DBP, and MAP with angiogenic factors are presented in . In the first trimester, sFlt1 levels were weakly correlated with SBP (rs=0.18, p=0.03) and MAP (rs=0.16, p=0.04). In the second trimester, sEng was weakly inversely correlated with MAP (rs= −0.17, p=0.05). Given these results, all analyses presented in and were repeated adjusting for blood pressure measurements, which were within the normal range for all patients. Adding SBP, DBP, or MAP measurements from the appropriate trimester to the analyses did not change the estimates or the significance of the associations reported in and (data not shown). sFlt1 in the first trimester was still weakly associated with first trimester SBP and MAP even when gestational age, and maternal age, BMI, and parity were added to the model, suggesting that the association of sFlt1 with first trimester blood pressure measures was in part independent from these other factors. Conversely, the association of sEng with MAP in second trimester was attenuated when BMI was added to the model.
Spearman correlations (rs) between blood pressure measures and maternal angiogenic factors measured in the same trimester in women who remained normotensive throughout pregnancy.