Effect of L-arginine supplementation in pregnant women with chronic hypertension and previous placenta vascular disorders receiving Aspirin prophylaxis: a randomized control trial.

Abstract

The aim of the study is to evaluate the effects of supplementation with Arginine (L-Arg) 3g, (together with Magnesium (Mg) 350 mg and Salicilate (Sal) 100 mg) on maternal blood pressure (BP), uterine artery doppler PI and neonatal outcomes in women with high-risk pregnancy for chronic hypertension (CH) and other previous placenta vascular disorders (PVD) already treated with low dose of aspirin (LDA), as recommended by guidelines. We enrolled women affected by CH and other previous PVD referred to the High-Risk Clinic of the Department of Maternal and Child's Health at the University Hospital of Modena and Reggio Emilia from September 2017 to June 2019. The study design was a controlled, randomized trial of oral supplementation of L-Arg 3g (together with Mg 350 mg and Sal extract 100 mg) + LDA 100 mg/day versus only LDA 100 mg/day. Inclusion criteria were: singleton pregnancy; diagnosis of chronic hypertension, previous preeclampsia <34 weeks, previous intrauterine growth restriction (IUGR) <10th centile or previous stillbirth (SB) related to placenta vascular disorders; gestational age <14 weeks. Each woman was enrolled between 12-14 weeks gestation and underwent 24-hour ambulatory BP monitoring with an automatic device (SpaceLab 92710, Critikon, WA), repeated at 18-20th and 24-26th weeks. Moreover Uterine artery Doppler ultrasound evaluation including PI were performed at 18-20 weeks gestation and repeated at 24-26th weeks. Pregnancy outcomes data were collected in a password protected database. Seventy-nine women agreed to participate in the study. No significant differences between the demographic characteristics in the two groups were found at enrolment (Group LDA + L-Arg: 30 patients versus Group LDA: 49 patients). In the LDA-L-Arg group there is no significant increase in both systolic (127.22±12.02 and 132.75±7.51 mmHg, P=0.002) and diastolic (75.85±8.53 and 83.63±6.05 mmHg, P=0.0000) BP values at 24-26 weeks reveled in the LDA group. The value of the uterine artery Doppler median PI>95th centile at 24-26 weeks show a significant reduction in the LDA+L-Arg group respect the LDA group (seven women, 23.3% vs. 21 women, 42.9%; P=0.04). A significantly lower percentage of women received new antihypertensive drugs in the LDA+ L-Arg group than the LDA group (6.7% vs. 24.5%) (P=0.02). There was neither statistically significant difference in perinatal outcomes between the two groups, except for trend of significance. Although we found only trends of improvements of perinatal outcomes in LDA+L-Arg group, considering the promising results on BP values, uterine artery PI and the low need to start a new antihypertensive treatment, thus the resulting impact in reducing pregnancy medicalization, number of maternal-fetal well-being monitoring visits and the need of induction of labor, we believe that further studies should be performed to enlarge our observation and clarify the role of L-Arg 3g supplementation as a protective integration in high-risk pregnancies already in prophylaxis with LDA.