Evidence map›Paper›PMID 26869377›Full record

Observational studyThe Lancet. Infectious diseases2016

Safety of artemisinins in first trimester of prospectively followed pregnancies: an observational study.

Kerryn A Moore, Julie A Simpson, Moo Kho Paw, MuPawJay Pimanpanarak, Jacher Wiladphaingern, Marcus J Rijken, Podjanee Jittamala, Nicholas J White, Freya J I Fowkes, François Nosten and 1 more

Erratum issuedOpen access · hybridAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Lancet. Infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 10 pooled it
11.5field-weighted citation impact, top 1% of its field
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

34 citing papers in PubMed, 10 syntheses or guidelines pooled it, 87 citations in OpenAlex.

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  8. The Vivax Surveyor: Online mapping database for Plasmodium vivax clinical trials.International journal for parasitology. Drugs and drug resistance · 2017
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 3 countries.

Kerryn A MooreCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, VIC, Australia. Electronic address: kerrynmoore.kam@burnet.edu.au.
Julie A SimpsonCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Moo Kho PawShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
MuPawJay PimanpanarakShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Jacher WiladphaingernShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Marcus J RijkenShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Podjanee JittamalaMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Nicholas J WhiteMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Freya J I FowkesCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine and Department of Infectious Diseases, Monash University, Melbourne, VIC, Australia.
François NostenShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Rose McGreadyShoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Shoklo Malaria Research Unit · THUniversity of Oxford · GBMahidol University · THBurnet Institute · AUMonash University · AUUniversity of Melbourne · AU

Funding

Wellcome Trust 093956
6 · The paper itself

Abstract

backgroundArtemisinins, the most effective antimalarials available, are not recommended for falciparum malaria during the first trimester of pregnancy because of safety concerns. Therefore, quinine is used despite its poor effectiveness. Assessing artemisinin safety requires weighing the risks of malaria and its treatment. We aimed to assess the effect of first-trimester malaria and artemisinin treatment on miscarriage and major congenital malformations.

methodsIn this observational study, we assessed data from antenatal clinics on the Thai-Myanmar border between Jan 1, 1994, and Dec 31, 2013. We included women who presented to antenatal clinics during their first trimester with a viable fetus. Women were screened for malaria, and data on malaria, antimalarial treatment, and birth outcomes were collected. The relationship between artemisinin treatments (artesunate, dihydroartemisinin, or artemether) and miscarriage or malformation was assessed using Cox regression with left-truncation and time-varying exposures.

findingsOf 55 636 pregnancies registered between 1994 and 2013, 25 485 pregnancies were analysed for first-trimester malaria and miscarriage, in which 2558 (10%) had first-trimester malaria. The hazard of miscarriage increased 1·61-fold after an initial first-trimester falciparum episode (95% CI 1·32-1·97; p<0·0001), 3·24-fold following falciparum recurrence (2·24-4·68; p<0·0001), and 2·44-fold (1·01-5·88; p=0·0473) following recurrent symptomatic vivax malaria. No difference was noted in miscarriage in first-line falciparum treatments with artemisinin (n=183) versus quinine (n=842; HR 0·78 [95% CI 0·45-1·34]; p=0·3645) or in risk of major congenital malformations (two [2%] of 109 [95% CI 0·22-6·47] versus eight (1%) of 641 [0·54-2·44], respectively).

interpretationFirst-trimester falciparum and vivax malaria both increase the risk of miscarriage. We noted no evidence of an increased risk of miscarriage or of major congenital malformations associated with first-line treatment with an artemisinin derivative compared with quinine. In view of the low efficacy of quinine and wide availability of highly effective artemisinin-based combination therapies, it is time to reconsider first-trimester antimalarial treatment recommendations.

fundingThe Wellcome Trust and The Bill & Melinda Gates Foundation.

Indexed as

Pregnancy Trimester, FirstAbortion, SpontaneousAdolescentAdultAntimalarialsArtemisininsFemaleHumansMalaria, FalciparumMalaria, VivaxPregnancyPregnancy ComplicationsQuinineThailandAntimalarialsartemisininArtemisininsartenimolQuinine

Identifiers

PMID26869377
PMCPMC4835584
OpenAlexW2261876003

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.