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Meta-Analysis
. 2007 Apr 18;2007(2):CD006490.
doi: 10.1002/14651858.CD006490.

Nitric oxide for preventing pre-eclampsia and its complications

S Meher  1 , L Duley
Affiliations
Meta-Analysis

Nitric oxide for preventing pre-eclampsia and its complications

S Meher et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: 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).

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).

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

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 1 Pre‐eclampsia.
1.2
1.2. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 2 Severe pre‐eclampsia.
1.3
1.3. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 3 HELLP syndrome.
1.4
1.4. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 4 Placental abruption.
1.5
1.5. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 5 Caesarean section.
1.6
1.6. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 6 Maternal side‐effects (subgroup by type of side‐effect).
1.7
1.7. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 7 Stopped treatment due to side‐effects.
1.8
1.8. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 8 Perinatal or neonatal death.
1.9
1.9. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 9 Preterm birth.
1.10
1.10. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 10 Small‐for‐gestational age.
1.11
1.11. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 11 Low Apgar score.
1.12
1.12. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 12 Admission to neonatal intensive care unit.
1.13
1.13. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 13 Respiratory distress syndrome.
1.14
1.14. Analysis
Comparison 1 Nitric oxide versus placebo/no intervention, Outcome 14 Intraventricular haemorrhage.
2.1
2.1. Analysis
Comparison 2 Nitric oxide versus nifedipine, Outcome 1 Pre‐eclampsia.
2.2
2.2. Analysis
Comparison 2 Nitric oxide versus nifedipine, Outcome 2 Severe hypertension.
2.3
2.3. Analysis
Comparison 2 Nitric oxide versus nifedipine, Outcome 3 Caesarean section.
2.4
2.4. Analysis
Comparison 2 Nitric oxide versus nifedipine, Outcome 4 Maternal side‐effects.
2.5
2.5. Analysis
Comparison 2 Nitric oxide versus nifedipine, Outcome 5 Perinatal death.
2.6
2.6. Analysis
Comparison 2 Nitric oxide versus nifedipine, Outcome 6 Preterm birth.
2.7
2.7. Analysis
Comparison 2 Nitric oxide versus nifedipine, Outcome 7 Small‐for‐gestational age.
3.1
3.1. Analysis
Comparison 3 Nitric oxide versus antiplatelet agents, Outcome 1 Progression of gestational hypertension.
3.2
3.2. Analysis
Comparison 3 Nitric oxide versus antiplatelet agents, Outcome 2 Placental abruption.
3.3
3.3. Analysis
Comparison 3 Nitric oxide versus antiplatelet agents, Outcome 3 Development or progression of renal failure.
3.4
3.4. Analysis
Comparison 3 Nitric oxide versus antiplatelet agents, Outcome 4 Death of baby.
3.5
3.5. Analysis
Comparison 3 Nitric oxide versus antiplatelet agents, Outcome 5 Preterm birth.
3.6
3.6. Analysis
Comparison 3 Nitric oxide versus antiplatelet agents, Outcome 6 Small‐for‐gestational age.
See this image and copyright information in PMC

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