The Association of High-Molecular-Weight Hyaluronic Acid (HMWHA), Alpha Lipoic Acid (ALA), Magnesium, Vitamin B6, and Vitamin D Improves Subchorionic Hematoma Resorption in Women with Threatened Miscarriage: A Pilot Clinical Study

Abstract

Background-We evaluated whether the oral intake of high-molecular-weight hyaluronic acid (HMWHA) in association with alpha lipoic acid (ALA), magnesium, vitamin B6, and vitamin D can improve the resorption of subchorionic hematoma in cases of threatened miscarriage. Methods-In this study, we enrolled 56 pregnant women with threatened miscarriage (i.e., subchorionic hematomas, pelvic pain/uterine contractions, and/or vaginal bleeding) between the 6th and the 13th week of gestation. They were treated with vaginal progesterone (200 mg/twice a day) (control group; n = 25) or vaginal progesterone plus oral 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6, and 50 mcg vitamin D (treatment group; n = 31; DAV^®-HA, LoLi Pharma srl, Rome, Italy). An ultrasound scan was performed at the first visit (T0) and after 7 days (T1) and 14 days (T2) until hematoma resorption. Results-At the ultrasound scan, the treatment group showed faster resorption of the subchorionic hematoma compared with the control group, both at T1 (control group 140 (112-180), treated group 84 (40-112), p < 0.0031), and T2 (control group: 72 (48-112), treated group: 0 (0-0), p < 0.0001). Moreover, subjective symptoms, such as vaginal bleeding, abdominal pain, and uterine contractions, showed a faster decrease in the treatment group than in the control group. Conclusions-The association may more rapidly improve the resolution of threatened miscarriage and related symptoms compared to the standard local protocol.

Keywords: HMWHA; resorption; subchorionic hematoma; threatened miscarriage; vaginal bleeding.

Figure 1

Flowchart of the study. A total of 56 pregnant women with threatened miscarriage, maternal age ≥18 and ≤50 years, and gestational age between 6th and 13th week were enrolled in this study. The control group (n = 25) was supplemented with vaginal suppositories of P4 (200 mg twice a day); the treatment group (n = 31) was supplemented with vaginal suppositories of P4 (200 mg twice a day) + HMWHA (200 mg) in combination with ALA (100 mg), magnesium (450 mg), vitamin B6 (2.6 mg), and vitamin D (50 mcg). A total of 3 patients discontinued the study (2 in the control group and 1 in the treatment group because of miscarriage). A total of 53 patients (n = 23 in the control group and n = 30 in the treatment group) completed the study and were included in the final analysis.

Figure 2

Representative ultrasounds of SCH (red arrow) of patients following or treatment with P4 (control group) (a–c) and HMWHA in association with ALA, magnesium, vitamin B6, and vitamin D (treatment group) (d–f). Ultrasound at T0, baseline; at T1 (1 week of treatment); at T2 (2 weeks of treatment). In the treatment group with HMWHA in association with ALA, magnesium, vitamin B6, and vitamin D, subchorionic hematoma (f) was no longer detectable at T2, unlike the control group (c). CRL = Crown-Rump Length.

Figure 3

Area (mm²) of hematoma resorption (SCH). The progress of subchorionic hematoma resorption was detected via ultrasound in the control group (n = 23; in light blue) and the treatment group (n = 30; in green) at different time points (T0, T1, T2). Mann–Whitney test was used to analyze variation in hematoma resorption between the group at T1 (p < 0.0031) and at T2 (p < 0.0001).