Prediction of preeclampsia utilizing the first trimester screening examination.

OBJECTIVE: To derive a prediction rule for preeclampsia and early onset preeclampsia requiring delivery <34 weeks using first trimester maternal, ultrasound, and serum markers. STUDY DESIGN: Prospective cohort study of women enrolled at first trimester screening. Maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women with preeclampsia and normal outcome. The prediction rule was derived by Lasso logistic regression analysis. RESULTS: In 2441 women, 108 (4.4%) women developed preeclampsia, and 18 (0.7%) early preeclampsia. Nulliparity, prior hypertension, diabetes, prior preeclampsia, mean arterial pressure, and the log pregnancy-associate pregnancy protein-A multiples of the median were primary risk factors. Prediction rules for preeclampsia/early preeclampsia had an area under the curve of 0.82/0.83 respectively. Preeclampsia was predicted with 49% sensitivity and early preeclampsia with 55% sensitivity for a 10% false positive rate. CONCLUSION: First trimester prediction rules using parameters currently available at first trimester screening identify a significant proportion of women with subsequent preeclampsia.

First-trimester prediction of small-for-gestational age neonates incorporating fetal Doppler parameters and maternal characteristics.

OBJECTIVE: First-trimester screening for subsequent delivery of a small-for-gestational-age (SGA) infant typically focuses on maternal risk factors and uterine artery (UtA) Doppler. Our aim is to test if incorporation of fetal umbilical artery (UA) and ductus venosus (DV) Doppler improves SGA prediction. STUDY DESIGN: Prospective screening study of singletons at 11-14 weeks. Maternal characteristics, serum concentrations of pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin are ascertained and UtA Doppler, UA, and DV Doppler studies are performed. These parameters are tested for their ability to predict subsequent delivery of a SGA infant. RESULTS: Among 2267 enrolled women, 191 (8.4%) deliver an SGA infant. At univariate analysis women with SGA neonates are younger, more frequently African-American (AA), nulliparous, more likely to smoke, have lower PAPP-A and free ß-human chorionic gonadotropin levels. They have a higher incidence of UtA Doppler bilateral notching, higher mean UtA Doppler-pulsatility index z-scores (P < .001) and UA pulsatility index z-scores (P = .03), but no significant difference in DV-pulsatility index z-scores or in the incidence of abnormal qualitative UA and DV patterns. Multivariate logistic regression analysis identifies nulliparity and AA ethnicity (P < .001), PAPP-A multiple of the median and bilateral notching (P < .05) as determinants of SGA infant. Predictive sensitivity was low; receiver operating characteristic curve analysis yields areas under the curve of 0.592 (95% confidence interval, 0.548-0.635) for the combination of UtA Doppler and UA pulsatility index z-scores. CONCLUSION: Delivery of a SGA infant is most frequent in nulliparous women of AA ethnicity. Despite the statistical association with UtA Doppler first-trimester SGA prediction is poor and not improved by the incorporation of fetal Doppler.

First-trimester angiopoietin-2: relationships with maternal and placental characteristics.

Angiopoietin-2 (Ang-2), synthesized by endothelial cells, is a marker of placental vascular remodeling. Ang-2 is expressed in the first trimester, and levels may therefore correlate to other parameters of placental vascular development. The aim of this study was to evaluate the relationships between Ang-2 and other maternal/placental factors in the first trimester. This was a prospective observational study of women presenting for first-trimester screening at 11 + 0 to 13 + 6 weeks. Consenting women underwent an ultrasound, physical examination, and blood draw. Maternal serum Ang-2 levels were determined using enzyme-linked immunosorbent assay. Results were evaluated with relation to maternal age, parity, race, body mass index (BMI), mean arterial pressure (MAP), smoking/caffeine use, and parameters of placental blood flow resistance. In 111 consecutive patients, serum Ang-2 ranged from 0.6 to 10.9 ng/mL. Ang-2 levels were unrelated to maternal age, race, parity, smoking, and caffeine intake. Significant negative correlations were observed with BMI (Pearson's R = -0.325; P < 0.0001) and MAP (Pearson's R = -0.287; P = 0.002). Ang-2 levels did not correlate with gestational age (Spearman's rho, 0.064; P = 0.5058), but a significant positive correlation with the crown-rump length was observed (Spearman's rho, 0.261; P = 0.006). Neither uterine artery notching nor umbilical artery Doppler parameters correlated with Ang-2 levels. We concluded that Ang-2 as a marker of placental angiogenesis has significant relationships with maternal risk factors associated with abnormal placental development.

Serum pentraxin-3 levels at 11 to 14 weeks' gestation: association with maternal and placental characteristics.

OBJECTIVE: Pentraxin (PTX)-3 is an inflammatory molecule that may be increased in the first trimester in pregnancies with subsequent preeclampsia. We measured first-trimester serum PTX-3 and correlated levels with maternal/placental factors related to placental development. STUDY DESIGN: Prospectively enrolled women had ultrasound, physical examination, and blood draw at 11-14 weeks. PTX-3 determined by enzyme-linked immunosorbent assay was related to maternal age, parity, race, body mass index (BMI), mean arterial blood pressure (MAP), smoking/caffeine, and uterine/umbilical artery Doppler pulsatility index (PI). RESULTS: In 111 patients PTX-3 levels ranged from 0.2-13.8 ng/mL. Spearman correlation between PTX-3 and gestational age (rho = 0.096), maternal age (rho = -0.049), BMI (rho = -0.07), MAP (rho = -0.085), mean uterine artery PI (rho = 0.150), and umbilical artery PI (rho = -0.021) was nonsignificant (all P > .05). Similarly, PTX-3 distribution was unaffected by smoking/caffeine use, BMI >30, MAP >100 mm Hg, or uterine artery notching (P > .05 for all). CONCLUSION: First-trimester PTX-3 is unrelated to maternal characteristics and placental Doppler.

First-trimester risk factors for preeclampsia development in women initiating aspirin by 16 weeks of gestation.

OBJECTIVE: The residual risk of preeclampsia in high-risk women on aspirin prophylaxis exceeds that of low-risk populations, and this study aimed to identify first-trimester maternal characteristics associated with aspirin prophylaxis failure. METHODS: This is a nested cohort study of prospectively enrolled women with verified initiation of risk-indicated aspirin prophylaxis by 16 weeks of gestation. First-trimester maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women who developed preeclampsia and those who did not. Blood pressure measurements were classified as prehypertension or hypertension according to the Joint National Committee on Hypertension guidelines. Chi square, nonparametric, and logistic regression analyses were used to determine the contributors to preeclampsia development. RESULTS: Six hundred fourteen women prospectively enrolled at 9-14 weeks of gestation initiated aspirin by 16 weeks of gestation. The 59 (9.6%) women who developed preeclampsia were more likely to have chronic hypertension, diabetes, and obesity and had higher first-trimester blood pressure and lower serum pregnancy-associated plasma protein-A concentrations (all P<.05). Having first-trimester Joint National Committee on Hypertension prehypertension or hypertension was associated with a 2.18-fold increased risk of developing preeclampsia, whereas normotension was associated with a reduction of risk of 56%. CONCLUSION: Women who develop preeclampsia while taking aspirin prophylaxis are more likely to have elevated first-trimester blood pressures. Conversely, first-trimester normotension is associated with a reduced risk of preeclampsia.

First trimester maternal characteristics, Doppler parameters and serum analytes after preeclampsia.

OBJECTIVE: To evaluate the impact of prior preeclampsia on first trimester assessment in subsequent pregnancy. METHODS: A total of 1283 parous patients were prospectively enrolled at 9-14 weeks of gestation. Maternal biophysical characteristics, ultrasound parameters and placental analytes were compared between women with and without prior preeclampsia. RESULTS: There is no association between prior preeclampsia and the first trimester ultrasound parameters or placental analytes studied. The effects of prior preeclampsia in subsequent pregnancy are exaggerated by increasing parity and are predominantly blood pressure-related, independent of other cardiovascular risk factors. CONCLUSION: There is a potential role for lifestyle modification and stricter pregnancy blood pressure control in patients with prior preeclampsia.