First-trimester miscarriage rate decreases with hydralazine therapy in pregnancies with early uterine vascular insufficiency: a cohort study

Abstract

Background

Miscarriage is the most frequent cause of pregnancy loss, affecting 15–20% of clinically recognized pregnancies. Early uterine vascular insufficiency (EUVI), defined as abnormal uterine artery (UA) Doppler impedance indices in early pregnancy, is present in two-thirds of pregnancies ending in miscarriage after embryonic cardiac activity has been detected. There is currently no available therapy for reducing the risk of miscarriage in these cases.

Objective

To determine whether vasodilator therapy with hydralazine can reduce abnormally high UA impedance indices and miscarriage rates in pregnancies with EUVI when administered from before 9 weeks’ gestation until completing 13 weeks’ gestation.

Methods

A total of 253 consecutive singleton pregnancies with a live embryo and scanned before 9 weeks’ gestation were included in the study. Ninety-two pregnancies (36.3%) were classified as having EUVI. Hydralazine was administered in daily doses of 50 mg, starting 24–36 h after the initial diagnosis of EUVI and continuing throughout the first trimester. The miscarriage rate in the hydralazine-treated EUVI group was compared with the one observed in our previously reported untreated cohort and the pregnancies with EUVI that declined treatment with hydralazine.

Results

The miscarriage rate among the hydralazine-treated EUVI group was significantly lower than the previously reported untreated cohort (7.8% versus 26.2%, p = .003; odds ratio (OR) = 4.3, 95% confidence interval (CI) = 1.6–11.9). In 15 untreated pregnancies with EUVI, the miscarriage rate was similar to that of the previously reported untreated cohort (26.7% versus 26.2%; p = .603) and higher than the hydralazine-treated group (26.7% versus 7.8%, p = .05; OR = 4.4, 95% CI = 1.1–18.2).

Conclusions

Hydralazine therapy in pregnancies with EUVI was associated with a significant decrease in the rate of miscarriage. We suggest a sequence of events leading to a higher risk of miscarriage in pregnancies with EUVI and propose a potential mechanism through which hydralazine may reduce this risk.

Keywords:

• Uterine artery
• Doppler ultrasound
• early uterine vascular insufficiency
• miscarriage
• hydralazine
• vasodilator therapy

Acknowledgements

The authors thank Jorge Rodriguez for the initial support with statistical analysis. RW passed away before the submission of the final version of this manuscript. SL accepts responsibility for the integrity and validity of the data collected and analyzed in this study. WS was supported by an unrestricted research grant from the Sociedad Profesional de Medicina Fetal ‘Fetalmed’ Ltda., Chile. The authors report no conflict of interest regarding the design, results, and conclusion in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.