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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.


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Association between first-line treatment of first-trimester falciparum malaria and miscarriage (n=1179)Models were adjusted for severity of the first falciparum malaria episode (asymptomatic, symptomatic, or hyperparasitaemic or severe), non-malaria febrile morbidity in the first trimester, and year of first consultation. See appendix p 9 for a table version of this figure, including univariable associations. *Hazard ratios are shown for treatments occurring before (<6 weeks’ gestation) and during (≥6 and <13 weeks’ gestation) the embryosensitive window. †Artemisinin rescue after quinine failure refers to artemisinin-based treatment in first trimester following failure of first-line treatment with quinine or quinine plus clindamycin. No miscarriages occurred in women who received artemisinin treatment after the embryo-sensitive window (≥13 and <14 weeks’ gestation). We did a subgroup analysis excluding women with asymptomatic malaria (n=919); the association between artemisinin treatment and miscarriage changed by <5% (appendix p 9). We did a subgroup analysis in women attending before 2007 whose gestational age was estimated from ultrasound biometry, because the accuracy of gestational age estimates affects the accuracy of the gestation time of antimalarial treatment, and quinine plus clindamycin succeeded quinine monotherapy in 2007 (n=469); associations were in the same direction but of greater magnitude (appendix p 9).
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fig4: Association between first-line treatment of first-trimester falciparum malaria and miscarriage (n=1179)Models were adjusted for severity of the first falciparum malaria episode (asymptomatic, symptomatic, or hyperparasitaemic or severe), non-malaria febrile morbidity in the first trimester, and year of first consultation. See appendix p 9 for a table version of this figure, including univariable associations. *Hazard ratios are shown for treatments occurring before (<6 weeks’ gestation) and during (≥6 and <13 weeks’ gestation) the embryosensitive window. †Artemisinin rescue after quinine failure refers to artemisinin-based treatment in first trimester following failure of first-line treatment with quinine or quinine plus clindamycin. No miscarriages occurred in women who received artemisinin treatment after the embryo-sensitive window (≥13 and <14 weeks’ gestation). We did a subgroup analysis excluding women with asymptomatic malaria (n=919); the association between artemisinin treatment and miscarriage changed by <5% (appendix p 9). We did a subgroup analysis in women attending before 2007 whose gestational age was estimated from ultrasound biometry, because the accuracy of gestational age estimates affects the accuracy of the gestation time of antimalarial treatment, and quinine plus clindamycin succeeded quinine monotherapy in 2007 (n=469); associations were in the same direction but of greater magnitude (appendix p 9).

Mentions: Of the 1207 women with first-trimester falciparum malaria, 1179 (98%) had a known first-line antimalarial treatment and a viable fetus at the time of treatment (figure 1). Most (842 [71%] of 1179) received first-line quinine (including quinine plus clindamycin), 129 (11%) of 1179 received first-line quinine followed by artemisinin (artemisinin rescue), 25 (2%) of 1179 received first-line mefloquine monotherapy, and 183 (16%) of 1179 received first-line artemisinin. First-line artemisinin treatment was not associated with miscarriage when compared with women who received first-line quinine only (HR 0·78 [95% CI 0·45–1·34]; p=0·3645; figure 4). Five (3%) of 183 women received two first-trimester artemisinin treatments; one miscarried, and four delivered.


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 first-line treatment of first-trimester falciparum malaria and miscarriage (n=1179)Models were adjusted for severity of the first falciparum malaria episode (asymptomatic, symptomatic, or hyperparasitaemic or severe), non-malaria febrile morbidity in the first trimester, and year of first consultation. See appendix p 9 for a table version of this figure, including univariable associations. *Hazard ratios are shown for treatments occurring before (<6 weeks’ gestation) and during (≥6 and <13 weeks’ gestation) the embryosensitive window. †Artemisinin rescue after quinine failure refers to artemisinin-based treatment in first trimester following failure of first-line treatment with quinine or quinine plus clindamycin. No miscarriages occurred in women who received artemisinin treatment after the embryo-sensitive window (≥13 and <14 weeks’ gestation). We did a subgroup analysis excluding women with asymptomatic malaria (n=919); the association between artemisinin treatment and miscarriage changed by <5% (appendix p 9). We did a subgroup analysis in women attending before 2007 whose gestational age was estimated from ultrasound biometry, because the accuracy of gestational age estimates affects the accuracy of the gestation time of antimalarial treatment, and quinine plus clindamycin succeeded quinine monotherapy in 2007 (n=469); associations were in the same direction but of greater magnitude (appendix p 9).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835584&req=5

fig4: Association between first-line treatment of first-trimester falciparum malaria and miscarriage (n=1179)Models were adjusted for severity of the first falciparum malaria episode (asymptomatic, symptomatic, or hyperparasitaemic or severe), non-malaria febrile morbidity in the first trimester, and year of first consultation. See appendix p 9 for a table version of this figure, including univariable associations. *Hazard ratios are shown for treatments occurring before (<6 weeks’ gestation) and during (≥6 and <13 weeks’ gestation) the embryosensitive window. †Artemisinin rescue after quinine failure refers to artemisinin-based treatment in first trimester following failure of first-line treatment with quinine or quinine plus clindamycin. No miscarriages occurred in women who received artemisinin treatment after the embryo-sensitive window (≥13 and <14 weeks’ gestation). We did a subgroup analysis excluding women with asymptomatic malaria (n=919); the association between artemisinin treatment and miscarriage changed by <5% (appendix p 9). We did a subgroup analysis in women attending before 2007 whose gestational age was estimated from ultrasound biometry, because the accuracy of gestational age estimates affects the accuracy of the gestation time of antimalarial treatment, and quinine plus clindamycin succeeded quinine monotherapy in 2007 (n=469); associations were in the same direction but of greater magnitude (appendix p 9).
Mentions: Of the 1207 women with first-trimester falciparum malaria, 1179 (98%) had a known first-line antimalarial treatment and a viable fetus at the time of treatment (figure 1). Most (842 [71%] of 1179) received first-line quinine (including quinine plus clindamycin), 129 (11%) of 1179 received first-line quinine followed by artemisinin (artemisinin rescue), 25 (2%) of 1179 received first-line mefloquine monotherapy, and 183 (16%) of 1179 received first-line artemisinin. First-line artemisinin treatment was not associated with miscarriage when compared with women who received first-line quinine only (HR 0·78 [95% CI 0·45–1·34]; p=0·3645; figure 4). Five (3%) of 183 women received two first-trimester artemisinin treatments; one miscarried, and four delivered.

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