Nitric oxide for preventing pre-eclampsia and its complications

Not enough evidence to say if nitric oxide donors or their precursors are helpful in preventing pre-eclampsia and its complications.

Pre-eclampsia is a serious complication of pregnancy occurring in about 10% of women. It is identified by increased blood pressure and protein in the urine, but women often suffer no symptoms initially. It can, through constriction of the blood vessels in the placenta, interfere with food and oxygen passing to the baby, thus inhibiting the baby's growth and causing the baby to be born too soon. Women can be affected by huge swelling and sometimes they go on to have fits. Nitric oxide drugs, like glycerol trinitrate, or their precursors, like L-arginine, may play a role in helping to prevent pre-eclampsia through their action in relaxing blood vessel walls. The review of trials found too few women had been studied, so it was not possible to say if nitric oxide drugs help prevent pre-eclampsia. However, these drugs did cause headaches, often sufficiently severe for women to stop taking the drugs. Future studies need to address these adverse effects and seek women's views.

Authors' conclusions: 

There is insufficient evidence to draw reliable conclusions about whether nitric oxide donors and precursors prevent pre-eclampsia or its complications.

[Note: The 13 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]

Read the full abstract...

Pre-eclampsia, a multisystem disorder of pregnancy characterised by high blood pressure and protein in the urine, is associated with endothelial dysfunction. Nitric oxide mediates many functions of the endothelium, including vasodilatation and inhibition of platelet aggregation. Pre-eclampsia may be associated with nitric oxide deficiency, but the evidence to support this suggestion is contradictory. Nevertheless, it has been hypothesised that agents which increase nitric oxide may prevent pre-eclampsia.


To assess the effectiveness and safety of nitric oxide donors and precursors for preventing pre-eclampsia and its complications.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2006), CENTRAL (The Cochrane Library 2006, Issue 3), and EMBASE (2002 to December 2004). We updated the search of the Pregnancy and Childbirth Group's Trials Register on 18 January 2010 and added the results to the awaiting classification section.

Selection criteria: 

Studies were included if they were randomised trials evaluating nitric oxide donors or precursors for preventing pre-eclampsia and its complications.

Data collection and analysis: 

Both review authors independently assessed studies for inclusion. Data were extracted and double checked for accuracy.

Main results: 

Six trials (310 women) were included. Four were of good quality and two were of uncertain quality. Four trials (170 women) compared nitric oxide donors (glyceryl trinitrate) or precursors (L-arginine) with either placebo or no intervention. There are insufficient data for reliable conclusions about the effects on pre-eclampsia (four trials, 170 women; relative risk (RR) 0.83, 95% confidence interval (CI) 0.49 to 1.41) or its complications. One trial (36 women) compared a nitric oxide donor with nifedipine, and another (76 women) compared it with antiplatelet agents. Both were too small for reliable conclusions about possible differential effects.

Glyceryl trinitrate was associated with an increased risk of headache (two trials, 56 women; RR 6.85, 95% CI 1.42 to 33.04), and of stopping treatment (two trials, 56 women; RR 4.02, 95% CI 1.15 to 14.09) compared to placebo. However, the increase for both outcomes was due to an extreme result in one small trial (7/7 versus 0/9 for both outcomes).