The PREG-Salt study is to evaluate the effect, safety and cost-effectiveness of low-sodium salt in reducing blood pressure and preventing hypertensive disorders in pregnant women at high risk in China. The study will recruit about 3,200 participants from approximately 100 hospitals across multiple provinces in China. Eligible pregnant women (≤16 weeks of gestation) will be randomly assigned in a 1:1 ratio to the following 2 groups:
1. Salt subsittute(intervention); 2. Usual salt (control) .
The intervention will last until delivery. The study employs an adaptive two-phase design. An interim analysis after the first phase (n=400) will inform whether the trial continues into the second phase and if any adjustments to the sample size are needed. The primary outcomes are:
Phase 1: The mean systolic blood pressure across antenatal visits (excluding the last week before delivery).
Phase 2: New-onset hypertensive disorders of pregnancy and related adverse events from randomization to delivery.
Singleton pregnancy with a viable fetus at ≤16 weeks of gestation.
Systolic Blood Pressure (SBP) ≥130 mmHg and <160 mmHg at enrollment, OR current monotherapy with antihypertensive medications such as labetalol or nifedipine (priority enrollment).
At least one of the following 4 items: advanced maternal age (≥35 years), pre-pregnancy obesity (BMI ≥28 kg/m²), history of preeclampsia, or pre-existing type 1 or type 2 diabetes.
At least two of the following 5 items: history of adverse pregnancy outcome (e.g., fetal death, placental abruption, fetal growth restriction), personal history of gestational hypertension or family history of preeclampsia (mother or sister), history of gestational diabetes, obstructive sleep apnea, or pre-pregnancy overweight (BMI 24-28 kg/m²).
SBP ≥160 mmHg or Diastolic Blood Pressure (DBP) ≥110 mmHg at enrollment.
Conditions or history associated with high uterine tension (e.g., polyhydramnios, macrosomia, hydatidiform mole); autoimmune diseases (e.g., systemic lupus erythematosus, antiphospholipid syndrome).
History of chronic kidney disease, OR any antenatal check-up with a confirmed estimated Glomerular Filtration Rate (eGFR) <70 ml/min/1.73m², OR dipstick urine protein ≥2+.
Diagnosed hyperkalemia.