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

Moore KA, Simpson JA, Paw MK, Pimanpanarak M, Wiladphaingern J, Rijken MJ, Jittamala P, White NJ, Fowkes FJ, Nosten F, McGready R - Lancet Infect Dis (2016)

Bottom Line: Artemisinins, 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre 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.

No MeSH data available.


Related in: MedlinePlus

Association between initial and recurrent first-trimester malaria and miscarriageModels include women lost to follow-up before 28 weeks (until gestation time last seen), but percentage calculations for delivered or miscarried do not. Models for falciparum malaria (1–4) include women that might have also had first-trimester vivax, malariae, or ovale malaria. See appendix p 8 for associations in women with only first-trimester falciparum malaria. Models for vivax malaria (5–6) exclude women who also had first-trimester falciparum malaria. Models 2 and 5 exclude women with symptomatic malaria. Models 3 and 6 exclude women with asymptomatic infections. Model 4 excludes women with uncomplicated infections. Models were adjusted for year (by stratification due to non-proportional hazards [p<0·001]), gravidity, current smoking status, and non-malaria febrile morbidity in first trimester. Age and previous miscarriage were omitted from multivariable models due to collinearity with gravidity. Adjusted results for gravidity, current smoking status, and febrile morbidity in first trimester are shown from Model 1. 146 women had recurrent first-trimester falciparum malaria (136 had two and ten had three episodes). 13 women had recurrent (two) asymptomatic first-trimester falciparum malaria. 81 women had recurrent symptomatic first-trimester falciparum malaria (75 had two, and six had three episodes). 17 women had recurrent (two episodes) asymptomatic fi0rst-trimester vivax malaria, and none miscarried. 38 women had recurrent (two) symptomatic first-trimester vivax malaria. See appendix p 8 for a table version of this figure, including univariable associations.
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fig3: Association between initial and recurrent first-trimester malaria and miscarriageModels include women lost to follow-up before 28 weeks (until gestation time last seen), but percentage calculations for delivered or miscarried do not. Models for falciparum malaria (1–4) include women that might have also had first-trimester vivax, malariae, or ovale malaria. See appendix p 8 for associations in women with only first-trimester falciparum malaria. Models for vivax malaria (5–6) exclude women who also had first-trimester falciparum malaria. Models 2 and 5 exclude women with symptomatic malaria. Models 3 and 6 exclude women with asymptomatic infections. Model 4 excludes women with uncomplicated infections. Models were adjusted for year (by stratification due to non-proportional hazards [p<0·001]), gravidity, current smoking status, and non-malaria febrile morbidity in first trimester. Age and previous miscarriage were omitted from multivariable models due to collinearity with gravidity. Adjusted results for gravidity, current smoking status, and febrile morbidity in first trimester are shown from Model 1. 146 women had recurrent first-trimester falciparum malaria (136 had two and ten had three episodes). 13 women had recurrent (two) asymptomatic first-trimester falciparum malaria. 81 women had recurrent symptomatic first-trimester falciparum malaria (75 had two, and six had three episodes). 17 women had recurrent (two episodes) asymptomatic fi0rst-trimester vivax malaria, and none miscarried. 38 women had recurrent (two) symptomatic first-trimester vivax malaria. See appendix p 8 for a table version of this figure, including univariable associations.

Mentions: Of 1207 women with first-trimester falciparum malaria, 165 (17% of 983 followed until 28 weeks') miscarried and 224 (19%) were lost to follow-up compared with 1963 (9%) of 20 978 and 1949 (9%) of 22 927 in women with no first-trimester malaria, respectively. In multivariable analyses, the hazard of miscarriage increased 1·61-fold (95% CI 1·32–1·97; p<0·0001) with an initial first-trimester falciparum malaria episode, and 3·24-fold (2·24–4·68; p<0·0001) with recurrent first-trimester falciparum malaria (figure 3). This association was stronger in women with symptomatic falciparum malaria than in women with asymptomatic falciparum malaria (figure 2). A single first-trimester hyperparasitaemic or severe falciparum malaria episode increased the hazard of miscarriage 4·21-fold (95% CI 2·43–7·29; p<0·0001; figure 3). An initial first-trimester vivax malaria episode, either asymptomatic or symptomatic, increased the hazard of miscarriage slightly (figure 3). Recurrent symptomatic first-trimester vivax malaria increased the hazard of miscarriage 2·44-fold (95% CI 1·01–5·88; p=0·0473; figure 3).


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

Moore KA, Simpson JA, Paw MK, Pimanpanarak M, Wiladphaingern J, Rijken MJ, Jittamala P, White NJ, Fowkes FJ, Nosten F, McGready R - Lancet Infect Dis (2016)

Association between initial and recurrent first-trimester malaria and miscarriageModels include women lost to follow-up before 28 weeks (until gestation time last seen), but percentage calculations for delivered or miscarried do not. Models for falciparum malaria (1–4) include women that might have also had first-trimester vivax, malariae, or ovale malaria. See appendix p 8 for associations in women with only first-trimester falciparum malaria. Models for vivax malaria (5–6) exclude women who also had first-trimester falciparum malaria. Models 2 and 5 exclude women with symptomatic malaria. Models 3 and 6 exclude women with asymptomatic infections. Model 4 excludes women with uncomplicated infections. Models were adjusted for year (by stratification due to non-proportional hazards [p<0·001]), gravidity, current smoking status, and non-malaria febrile morbidity in first trimester. Age and previous miscarriage were omitted from multivariable models due to collinearity with gravidity. Adjusted results for gravidity, current smoking status, and febrile morbidity in first trimester are shown from Model 1. 146 women had recurrent first-trimester falciparum malaria (136 had two and ten had three episodes). 13 women had recurrent (two) asymptomatic first-trimester falciparum malaria. 81 women had recurrent symptomatic first-trimester falciparum malaria (75 had two, and six had three episodes). 17 women had recurrent (two episodes) asymptomatic fi0rst-trimester vivax malaria, and none miscarried. 38 women had recurrent (two) symptomatic first-trimester vivax malaria. See appendix p 8 for a table version of this figure, including univariable associations.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835584&req=5

fig3: Association between initial and recurrent first-trimester malaria and miscarriageModels include women lost to follow-up before 28 weeks (until gestation time last seen), but percentage calculations for delivered or miscarried do not. Models for falciparum malaria (1–4) include women that might have also had first-trimester vivax, malariae, or ovale malaria. See appendix p 8 for associations in women with only first-trimester falciparum malaria. Models for vivax malaria (5–6) exclude women who also had first-trimester falciparum malaria. Models 2 and 5 exclude women with symptomatic malaria. Models 3 and 6 exclude women with asymptomatic infections. Model 4 excludes women with uncomplicated infections. Models were adjusted for year (by stratification due to non-proportional hazards [p<0·001]), gravidity, current smoking status, and non-malaria febrile morbidity in first trimester. Age and previous miscarriage were omitted from multivariable models due to collinearity with gravidity. Adjusted results for gravidity, current smoking status, and febrile morbidity in first trimester are shown from Model 1. 146 women had recurrent first-trimester falciparum malaria (136 had two and ten had three episodes). 13 women had recurrent (two) asymptomatic first-trimester falciparum malaria. 81 women had recurrent symptomatic first-trimester falciparum malaria (75 had two, and six had three episodes). 17 women had recurrent (two episodes) asymptomatic fi0rst-trimester vivax malaria, and none miscarried. 38 women had recurrent (two) symptomatic first-trimester vivax malaria. See appendix p 8 for a table version of this figure, including univariable associations.
Mentions: Of 1207 women with first-trimester falciparum malaria, 165 (17% of 983 followed until 28 weeks') miscarried and 224 (19%) were lost to follow-up compared with 1963 (9%) of 20 978 and 1949 (9%) of 22 927 in women with no first-trimester malaria, respectively. In multivariable analyses, the hazard of miscarriage increased 1·61-fold (95% CI 1·32–1·97; p<0·0001) with an initial first-trimester falciparum malaria episode, and 3·24-fold (2·24–4·68; p<0·0001) with recurrent first-trimester falciparum malaria (figure 3). This association was stronger in women with symptomatic falciparum malaria than in women with asymptomatic falciparum malaria (figure 2). A single first-trimester hyperparasitaemic or severe falciparum malaria episode increased the hazard of miscarriage 4·21-fold (95% CI 2·43–7·29; p<0·0001; figure 3). An initial first-trimester vivax malaria episode, either asymptomatic or symptomatic, increased the hazard of miscarriage slightly (figure 3). Recurrent symptomatic first-trimester vivax malaria increased the hazard of miscarriage 2·44-fold (95% CI 1·01–5·88; p=0·0473; figure 3).

Bottom Line: Artemisinins, 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.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.

View Article: PubMed Central - PubMed

Affiliation: Centre 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.

No MeSH data available.


Related in: MedlinePlus