Evidence map›Paper›PMID 39800868›Full record

SynthesisBJOG : an international journal of obstetrics and gynaecology2025

L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis.

Maureen Makama, Annie R A McDougall, Jenny Cao, Kate Mills, Phi-Yen Nguyen, Roxanne Hastie, Anne Ammerdorffer, A Metin Gülmezoglu, Joshua P Vogel

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BJOG : an international journal of obstetrics and gynaecology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Therapeutic Interventions for Preeclampsia: Integrating Placental and Maternal Perspectives.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Maureen MakamaWomen's, Children's and Adolescents' Health Program, Burnet Institute, Melbourne, Australia.ORCID https://orcid.org/0000-0002-4164-3702
Annie R A McDougallWomen's, Children's and Adolescents' Health Program, Burnet Institute, Melbourne, Australia.ORCID https://orcid.org/0000-0003-1182-6679
Jenny CaoWomen's, Children's and Adolescents' Health Program, Burnet Institute, Melbourne, Australia.ORCID https://orcid.org/0000-0001-7643-8277
Kate MillsWomen's, Children's and Adolescents' Health Program, Burnet Institute, Melbourne, Australia.ORCID https://orcid.org/0009-0003-6262-7220
Phi-Yen NguyenWomen's, Children's and Adolescents' Health Program, Burnet Institute, Melbourne, Australia.ORCID https://orcid.org/0000-0002-0476-3385
Roxanne HastieDepartment of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Australia.ORCID https://orcid.org/0000-0002-4342-1943
Anne AmmerdorfferConcept Foundation, Geneva, Switzerland.ORCID https://orcid.org/0000-0002-1059-061X
A Metin GülmezogluConcept Foundation, Geneva, Switzerland.ORCID https://orcid.org/0000-0003-4674-0998
Joshua P VogelWomen's, Children's and Adolescents' Health Program, Burnet Institute, Melbourne, Australia.ORCID https://orcid.org/0000-0002-3214-7096

Funding

Bill and Melinda Gates FoundationPerpetual Impact Philanthropy grant
6 · The paper itself

Abstract

backgroundEvidence suggests L-arginine may be effective at reducing pre-eclampsia and related outcomes. However, whether L-arginine can prevent or only treat pre-eclampsia, and thus the target population and timing of initiation, remains unknown.

objectivesTo evaluate the effects of L-arginine and L-citrulline (precursor of L-arginine) on the prevention and treatment of pre-eclampsia. SEARCH STRATEGY: MEDLINE, Embase, CINAHL, Global Index Medicus and the Cochrane Library were searched through 7 February 2024. SELECTION CRITERIA: Trials administering L-arginine or L-citrulline to pregnant women, with the comparison group receiving placebo or standard care, were included. DATA COLLECTION AND ANALYSIS: Meta-analyses were conducted separately for prevention or treatment trials, using random-effects models. MAIN

resultsTwenty randomised controlled trials (RCTs) (2028 women) and three non-randomised trials (189 women) were included. The risk of bias was 'high' in eight RCTs and showed 'some concerns' in 12. In prevention trials, L-arginine was associated with a reduced risk of pre-eclampsia (relative risk [RR] 0.52; 95% confidence interval [CI], 0.35, 0.78; low-certainty evidence, four trials) and severe pre-eclampsia (RR 0.23; 95% CI, 0.09, 0.55; low-certainty evidence, three trials). In treatment trials, L-arginine may reduce mean systolic blood pressure (MD -5.64 mmHg; 95% CI, -10.66, -0.62; very low-certainty evidence, three trials) and fetal growth restriction (RR 0.46; 95% CI, 0.26, 0.81; low-certainty evidence, two trials). Only one study (36 women) examined L-citrulline and reported no effect on pre-eclampsia or blood pressure.

conclusionsL-arginine may be promising for pre-eclampsia prevention and treatment, but findings should be interpreted cautiously. More trials are needed to determine the optimal dose and time to commence supplementation and support clinical decision-making.

Indexed as

ArginineCitrullinePre-EclampsiaFemaleHumansPregnancyRandomized Controlled Trials as TopicArginineCitrullinehypertensive disorders of pregnancyL‐arginineL‐citrullinepre‐eclampsiapregnant women

Identifiers

PMID39800868
PMCPMC11969923

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.