Role of first‐trimester umbilical vein blood flow in predicting large‐for‐gestational age at birth

Objectives To describe umbilical vein (UV) hemodynamics at 11 + 0 to 13 + 6 weeks of gestation in pregnancies delivering a large‐for‐gestational‐age (LGA) neonate, and to build a multiparametric model, including pregnancy and ultrasound characteristics in the first trimester, that is able to predict LGA at birth. Methods This was a matched case–control study, of singleton pregnancies that underwent ultrasound examination at 11 + 0 to 13 + 6 weeks for aneuploidy screening, at a single center over a 4‐year period. Cases were women who delivered a neonate with birth weight (BW) > 90 th centile for gestational age and sex, according to local birth‐weight standards, while controls were those who delivered a neonate with BW ranging between the 10 th and 90 th centiles, matched for maternal and gestational age, at a ratio of 1:3. Each included case underwent Doppler assessment of the uterine arteries and UV, including measurement of its diameter, time‐averaged maximum velocity (TAMXV) and UV blood flow (UVBF). UVBF and its components were expressed as Z ‐scores. Fisher's exact test and Mann–Whitney U ‐test were used to compare differences in maternal biomarkers and ultrasound characteristics between pregnancies complicated by LGA and controls. Logistic regression and receiver‐operating‐characteristics (ROC) curve analyses were carried out to identify independent predictors of LGA and to build a multiparametric prediction model integrating different maternal, pregnancy and ultrasound characteristics. Subgroup analysis was also performed, considering women who delivered a neonate with BW > 4000 g. Results In total, 964 pregnancies (241 with LGA at birth and 723 without) were included in the study. In LGA pregnancies compared with controls, UV‐TAMXV Z ‐score (0.8 (interquartile range (IQR), 0.4–1.5) vs 0.0 (IQR, −0.3 to 0.5); P  ≤ 0.001) and UVBF Z ‐score (1.3 (IQR, 0.8–1.9) vs 0.1 (IQR, −0.4 to 0.4); P  ≤ 0.001) were higher, while there was no difference in median UV diameter Z ‐score ( P  = 0.56). Median uterine artery pulsatility index multiples of the median (MoM; 0.94 (IQR, 0.78–1.12) vs 1.02 (IQR, 0.84–1.19); P  = 0.04) was significantly lower in LGA pregnancies. On multivariate logistic regression analysis, maternal body mass index (BMI; adjusted odds ratio (aOR), 1.2 (95% CI, 1.1–1.7); P  < 0.001), parity (aOR, 1.4 (95% CI, 1.2–1.6); P  < 0.001), pregnancy‐associated plasma protein‐A (PAPP‐A) MoM (aOR, 1.1 (95% CI, 1.0–1.6); P  = 0.04) and UVBF Z ‐score (aOR, 1.6 (95% CI, 1.1–1.9); P  < 0.001) were associated independently with LGA. A multiparametric model integrating parity, BMI and PAPP‐A MoM provided an area under the ROC curve (AUC) of 0.72 (95% CI, 0.67–0.76) for the prediction of LGA. The addition of UVBF Z ‐score to this model significantly improved the prediction of LGA provided by maternal and biochemical factors, with an AUC of 0.79 (95% CI, 0.75–0.83; P  = 0.03). Similarly, the model incorporating UVBF Z ‐score predicted BW > 4000 g with an AUC of 0.83 (95% CI, 0.75–0.93). Conclusions UVBF measured at the time of the 11–14‐week scan is associated independently with, and is predictive of, LGA and BW > 4000 g. Adding measurement of UVBF to a multiparametric model that includes maternal (parity and BMI) and biochemical (PAPP‐A) parameters improves the diagnostic accuracy of prenatal screening for LGA at birth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.