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Objective To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. Design A nested case–control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. Setting A multicentre study in 16 academic medical centres in the USA. Population Low-risk nulliparous women. Methods Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9–12, 15–18 and 23–26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. Main outcome measures Change in PlGF, sFlt-1 and sEng. Results Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64–99%), 77% (95% CI 50–93%) and 77% (95%CI 50–93%) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. Conclusion Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

Background Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. Objective To determine the utility of early second trimester uterine artery Doppler studies as a predictor of small for gestational age (SGA) neonates. Study Design Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at eight institutions across the United States. Participants were seen at three study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days and 22 weeks 6 days gestation. Test characteristics for varying thresholds in the prediction of SGA (defined as birth weight <5th percentile for gestational age [Alexander growth curve]) were evaluated. Results Uterine artery Doppler indices, birth weight, and gestational age at birth were available for 8,024 women. Birth weight <5th percentile for gestational age occurred in 358 (4.5 percent) of the births. Typical thresholds for the uterine artery Doppler indices were all associated with birth weight <5th percentile for gestational age (P<0.0001 for each), but the positive predictive values for these cutoffs were all <15 percent and areas under receiver operating characteristic curves (AUCs) ranged from 0.50 to 0.60. Across the continuous scales for these measures, the AUCs ranged from 0.56 to 0.62. Incorporating maternal age, early pregnancy BMI, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pre-gestational diabetes in the prediction model resulted in only modest improvements in the AUCs ranging from 0.63 to 0.66. Conclusion In this large prospective cohort, early second trimester uterine artery Doppler studies were not a clinically useful test for predicting SGA babies.

IMPORTANCE Despite the increasing prevalence of pregravid obesity, systematic evaluation of the association of maternal obesity with fetal growth trajectories is lacking.OBJECTIVE To characterize differences in fetal growth trajectories between obese and nonobese pregnant women, and to identify the timing of any observed differences. DESIGN, SETTING, AND PARTICIPANTSThe Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons study enrolled cohorts of pregnant women at 12 US health care institutions. Obese women (with prepregnancy body mass index > 30) and nonobese women (prepregnancy body mass indexes, 19-29.9) without major chronic diseases were recruited between 8 weeks and 0 days' gestation and 13 weeks and 6 days' gestation. A mixed longitudinal randomization scheme randomized participants into 1 of 4 schedules for 2-dimensional and 3-dimensional ultrasonograms to capture weekly fetal growth data throughout the remainder of their pregnancies. MAIN OUTCOMES AND MEASURESOn each ultrasonogram, fetal humerus length, femur length, biparietal diameter, head circumference, and abdominal circumference were measured. Fetal growth curves were estimated using linear mixed models with cubic splines. Median differences in the fetal measures at each gestational week of the obese and nonobese participants were examined using the likelihood ratio and Wald tests after adjustment for maternal characteristics. RESULTSThe study enrolled 468 obese and 2334 nonobese women between 8 weeks and 0 days' gestation and 13 weeks and 6 days' gestation. After a priori exclusion criteria, 443 obese and 2320 nonobese women composed the final cohort. Commencing at 21 weeks' gestation, femur length and humerus length were significantly longer for fetuses of obese woman than those of nonobese women. Differences persisted in obese and nonobese groups through 38 weeks' gestation (median femur length, 71.0 vs 70.2 mm; P = .01; median humerus length, 62.2 vs 61.6 mm; P = .03). Averaged across gestation, head circumference was significantly larger in fetuses of obese women than those of nonobese women (P = .02). Fetal abdominal circumference was not greater in the obese cohort than in the nonobese cohort but was significantly larger than in fetuses of normal-weight women (with body mass indexes between 19.0-24.9) commencing at 32 weeks (median, 282.1 vs 280.2 mm; P = .04). Starting from 30 weeks' gestation, estimated fetal weight was significantly larger for the fetuses of obese women (median, 1512 g [95% CI, 1494-1530 g] vs 1492 g [95% CI, 1484-1499 g]) and the difference grew as gestational age increased. Birth weight was higher by almost 100 g in neonates born to obese women than to nonobese women (mean, 3373.2 vs 3279.5 g). CONCLUSIONS AND RELEVANCEAs early as 32 weeks' gestation, fetuses of obese women had higher weights than fetuses of nonobese women. The mechanisms and long-term health implications of these findings are not yet established.

Since the last survey, >10 years ago, chorionic villus sampling training has declined further. A decrease in the number of procedures that are performed is the leading barrier to this training.