Longitudinal fetal growth parameters in women at high risk for pre-eclampsia

Abstract

Objectives: To evaluate longitudinal changes in fetal growth parameters, umbilical artery (UA) Doppler measurements and amniotic fluid index (AFI) in East Asian pregnant women who underwent screening for preterm pre-eclampsia (PE) in the first trimester, and to evaluate correlations of these variables with first-trimester biomarkers.

Methods: This was a prospective, longitudinal, nested case-control study of women with a singleton pregnancy who participated in the first-trimester screen-and-prevent program for preterm PE at the Prince of Wales Hospital, Hong Kong SAR, China, between January 2020 and December 2023. The risk of developing preterm PE was determined using the Fetal Medicine Foundation first-trimester triple test. High-risk women (adjusted risk ≥ 1:100) were administered a daily dose of aspirin at either 100 mg or 160 mg according to maternal weight, starting before 16 weeks and continuing until 36 weeks' gestation, or earlier than 36 weeks in the case of delivery or development of PE. Low-risk women were matched based on maternal age, weight and the calendar date of enrolment. Biomarkers including mean arterial pressure, uterine artery (UtA) pulsatility index (PI) and placental growth factor (PlGF) were measured at the recruitment visit. Participants were followed up at 20 + 0 to 24 + 6 weeks and 30 + 0 to 37 + 6 weeks to measure fetal biparietal diameter, head circumference, abdominal circumference, femur length, estimated fetal weight, UA-PI and AFI. Multilevel linear mixed-effects modeling was used to assess longitudinal changes in fetal growth parameters, UA-PI and AFI. Pearson's coefficient was used to assess the correlation of first-trimester biomarkers with fetal growth parameters, UA-PI and AFI.

Results: Our cohort comprised 509 low-risk women who did not develop PE, 1879 high-risk women who did not develop PE and 184 high-risk women who developed PE. At midgestation, mean Z-scores of most fetal growth parameters were significantly lower in the high-risk women who developed PE compared with those of the other groups. This pattern persisted into late gestation. AFI was consistently lower in high-risk pregnancies, with the greatest decrease between visits observed in those who developed PE. High-risk women who developed PE had the highest mean UA-PI Z-score at mid-gestation, which decreased by late gestation but remained elevated compared with the other two groups. UtA-PI was correlated negatively with fetal growth parameters, while PlGF showed a positive correlation with fetal growth parameters.

Conclusions: Differences in fetal growth, UA-PI and AFI exist between women identified as low vs high risk for preterm PE based on first-trimester screening, especially in high-risk women who develop PE. These findings are evident as early as the second trimester and persist into the third trimester. This highlights the need for a structured antenatal management plan with fetal monitoring in high-risk cases, irrespective of aspirin prophylaxis. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Keywords: amniotic fluid index; biomarker; fetal growth; longitudinal analysis; pre‐eclampsia; umbilical artery pulsatility index.