P-390 Serum homocysteine and uterine artery Doppler ultrasound in combination has better predictive accuracy in women with preeclampsia: useful tool for early screening in everyday practice
Authors: Kalapahar S , Chakraborty P , Shama S , Mitra I , Chattopadhyay R , Ghosh S , Chakraborty M , Chakravarty B 
Published: June 2022

Abstract

Study question
Is serum homocysteine combined with uterine-artery Doppler were effective in predicting preeclampsia (≥140mmHg/≥90mmHg blood pressure) in singleton pregnancy during 11–15 weeks of gestation?

Summary answer
Combination of serum homocysteine levels with uterine-artery Doppler is superior to individual presence of biochemical/ultrasound marker/s making the duo effective for early screening in preeclampsia.

What is known already
American College of Obstetricians and Gynecologists and National Institute for Care and Health Excellence recommend identifying patients who are at high risk of developing preeclampsia based on medical history. Recently, biochemical and ultrasound markers were investigated for prediction of preeclampsia, but none of them were predictably reliable, valid, and suitable for routine clinical use. Increased levels of homocysteine in 1st-trimester, seems to signal onset of preeclampsia later in pregnancy portraying severity of the disease as well. We aimed to identify predictive value of serum homocysteine combined with uterine-artery Doppler in singleton pregnancy during 11–15 weeks of gestation for preeclampsia.

Study design, size, duration
One hundred forty-two consented singleton pregnant women (28-45 years) at gestational age of 11–15 weeks, recruited between January to December 2021 from Institute of Reproductive Medicine, Kolkata were enrolled in the study. Women who used aspirin as a prophylaxis for preeclampsia or were diagnosed to have fetal, structural or chromosomal abnormalities were excluded from the study (n = 7). Maternal age, weight and height, mean arterial pressure, parity, and obstetric history were documented.

Participants/materials, setting, methods
Uterine-artery Doppler ultrasound and serum homocysteine levels were performed transabdominally and using ELISA respectively. Pregnancy outcomes were recorded. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at optimal cut-off values were determined to predict preeclampsia. Optimal cut-off values for homocysteine levels were calculated using receiver operator characteristic curve (ROC). Chi-square test, Fisher’s exact test, unpaired t test, and Mann–Whitney U test were used when appropriate. P-value &lt;0.05 was considered statistically significant.

Main results and the role of chance
16 cases had preeclampsia (11.26%) of whom 9 had early-onset preeclampsia (6.33%). Baseline characteristics including maternal-age (&gt;35 or&lt;), parity, body-mass- index, and gestational-age at measurement were not significantly different between two groups excepting higher (p &lt; 0.001) mean arterial blood pressure (mmHg) at first trimester (97.2±6.4 vs. 81.1±7.2) in preeclampsia. Preeclamptic women had significantly higher (p &lt; 0.001) serum homocysteine levels (μmol/l) (26.1±3.5 vs 10.2± 5.6) than normotensive pregnant women (n = 119). No difference in mean pulsatility (PI) of uterine-artery was observed (1.78±0.64 vs. 1.72±0.48) excluding significantly high (p &gt; 0.02) in women with early-onset preeclampsia than control (2.11±0.81 vs. 1.39±0.92). However, lower (p &lt; 0.01) gestational age (weeks) (35.4±2.1 vs. 37.6±1.4), and neonatal birth weight (gms) (2937.3±578.2 vs. 3227.6±421.5) with higher (p &lt; 0.001) preterm delivery (25% vs 5.04%), low birth weight (25% vs 5.04%) and neonatal respiratory distress syndrome (12.5% vs. 0.84%) was documented in preeclampsia than control/s. The optimal cut-off value of serum homocysteine with PI levels, from ROC (AUC=0.735, p &lt; 0.001) was superior to individual ROC (AUC=0.451; AUC=0.268). The sensitivity, specificity, PPV, and NPV were 67.7%, 70.5%, 1.7%, and 98.5%, respectively using a combination of abnormal serum homocysteine levels with abnormal uterine artery Doppler PI (above 95th percentile) and used as a predictive value for preeclampsia.

Limitations, reasons for caution
The limitation of this study was that there were small cases of early-onset preeclampsia. Additional studies with a larger sample size of early-onset preeclampsia and other models using serum homocysteine, combined with uterine artery Doppler, and maternal characteristic risk factors should be conducted.

Wider implications of the findings
Early screening of preeclampsia by using combination of serum homocysteine and uterine artery Doppler during first trimester (11–15 weeks) at the same visit may be more effective and allows the timing for using early low-dose aspirin prophylaxis in order to prevent preeclampsia.

Trial registration number
Not applicable