The incidence of hypertensive disease (HDP) in pregnancy is about 1/10, covering chronic hypertension, gestational hypertension and preeclampsia, and if not well controlled, it can lead to serious consequences such as hypertensive crisis, eclampsia, stroke and even maternal and infant death. Oral antihypertensive drugs are a key means to prolong gestational age and reduce the risk of adverse outcomes, and three drugs are currently commonly used in clinical practice, but there has been a lack of clear consensus on the efficacy and safety differences between the three. A network meta-analysis published in the American Journal of Obstetrics and Gynecology in October 2025 provides the latest evidence-based basis for clinical selection of these three drugs by integrating data from 23 randomized controlled trials.
Three commonly used oral antihypertensive drugs
1. Methyldopa
Mechanism of action: α₂ receptor agonist, achieving mild blood pressure reduction through central regulation.
Clinical positioning: Traditional classic drugs, with long clinical application time, are one of the common choices during pregnancy.
2. Labetalol
Mechanism of action: α. β receptor antagonist, which has dual antihypertensive effect and has a fast effect.
Clinical positioning: At present, it is widely used and is suitable for many types of gestational hypertension, which is more advantageous for patients with fast heart rate.
3. Nifedipine
Mechanism of action: Calcium channel blocker, direct dilation of blood vessels to lower blood pressure, direct antihypertensive effect.
Clinical positioning: In the past ten years, it has been included in the guidelines for antihypertension during pregnancy, which is a commonly used first-line drug, especially suitable for vasospasm-related hypertension.
Core findings: Efficacy versus safety
The study included 23 randomized controlled trials involving 3989 pregnant women, with the following core results analysed through a pool of direct and indirect evidence:
1. Primary outcome: Prevention and control of severe hypertension
❖Labetalol and methyldopa significantly reduced the incidence of severe hypertension compared with placebo/no treatment (labetalol RR=0.20, 95% CI 0.09-0.48; methyldopa RR=0.44, 95% CI 0.20-0.99).
❖ When the three drugs were directly compared, none of them were found to have significant advantages in preventing and controlling severe hypertension; There was no statistically significant difference between nifedipine and placebo/no treatment (which may be related to insufficient direct comparison data).
2. Key secondary outcomes: maternal and infant safety indicators
Preeclampsia: Labetalol was superior to nifedipine and reduced the risk of preeclampsia by 50% (RR=0.50, 95% CI 0.28-0.87); There was no significant difference between methyldopa and labetalol and nifedipine.
Preterm birth (<37 weeks): Labetalol versus nifedipine significantly reduced the risk of preterm birth (RR=0.68, 95% CI 0.52 to 0.90); There was no statistical difference between other drugs.
Febrile/neonatal related: There were no significant differences between the three drugs in neonatal birth weight, low birth weight (<2500g), small for gestational age (<10th percentile), neonatal mortality, and 5-minute Apgar score ≤7.
Other maternal and infant complications: HELLP syndrome, stroke, liver hemorrhage, eclampsia and other serious complications are too low, and no difference between drugs is found; The three drugs had no significant effect on maternal mortality.
3. Special populations and subgroups
❖ In patients with different types of hypertension (chronic hypertension, gestational hypertension, preeclampsia), the efficacy trend of the three drugs was the same, and there was no significant subgroup difference.
❖ No significant differences were found between the three drugs in the outcome of severe preterm birth (<34 weeks).
Clinical selection suggestion: Accurately match different scenarios
1. Preferential selection of the case of labetalol
❖ Pregnant women with high risk of preeclampsia (such as past medical history, increased blood pressure in the first trimester);
❖ People who need to reduce the risk of preterm birth (such as small gestational age and immature fetal development);
❖ For pregnant women with high blood pressure with a fast heart rate, the β receptor antagonism effect of labetalol can take into account heart rate control
2. Preferential treatment of methyldopa is preferred
❖ Pregnant women with contraindications to labetalol or nifedipine;
❖ Patients with chronic hypertension who have used methyldopa before pregnancy and have stable blood pressure control can continue to use it;
❖ Pregnant women with no significant increase in blood pressure and need to lower blood pressure mildly.
3. Preferential treatment of nifedipine
❖ Alternative options when the other two drugs are not effective in lowering blood pressure;
❖ Hypertension associated with vasospasm (such as early manifestations of preeclampsia);
❖ Pregnant women with intolerance to β receptor antagonists (such as a history of asthma).
4. General precautions
There is no absolute superiority or disadvantage: all three drugs can effectively control blood pressure, and the core difference is only reflected in the prevention and control of preeclampsia and preterm birth risk, and none of the drugs are fully victorious in all outcomes.
Individualized monitoring: Regardless of which drug is chosen, it is necessary to monitor blood pressure regularly (the target is mostly < 140/90mmHg), and pay attention to fetal growth and development.
Avoid unauthorized adjustment: The dosage adjustment of the drug should be made gradually by the doctor according to the changes in blood pressure, and the drug should not be stopped or changed by himself.
Study limitations and clinical tips
1. Limitations
Quality of the evidence: The overall quality of the included studies was low to moderate, with some studies having problems such as unclear randomisation and inconsistent outcome definitions.
Data limitations: Some serious complications (such as eclampsia and maternal death) cannot be effectively analyzed due to the low incidence rate.
Population differences: The impact of factors such as race and comorbidities on drug response is not fully considered, and there may be differences in efficacy among different populations
2. Clinical tips
Do not blindly pursue the "best drug": clinical decision-making should be based on the characteristics of pregnant women's blood pressure, comorbidities, gestational age and doctors' experience, rather than relying solely on drug efficacy data;
Pay attention to basic interventions: antihypertensive drugs cannot replace basic interventions such as low-salt diet, moderate exercise, and regular work and rest, and need to be jointly managed by multiple means;
Beware of abnormal signals: If there is a sudden increase in blood pressure, headache, blurred vision, fetal growth retardation, etc. during medication, you need to seek medical attention immediately for evaluation
The oral antihypertensive drugs methyldopa, labetalol and nifedipine during pregnancy are effective in controlling severe hypertension and ensuring the core safety of the fetus, and there is no absolute advantage or disadvantage. However, labetalol is slightly better than nifedipine in reducing the risk of preeclampsia and preterm birth, and can be used as a preferred choice for high-risk groups. In clinical application, it is necessary to abandon the "one-size-fits-all" mentality, formulate personalized plans according to the individual conditions of pregnant women, and strengthen pregnancy monitoring to ensure the safety of mother and baby to the greatest extent.
责编：Lucy