cgp-56697 and Abortion--Spontaneous

Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy.. For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371.. We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92).. We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.. Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Topics: Abortion, Spontaneous; Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Drug Combinations; Ethanolamines; Female; Humans; Malaria; Malaria, Falciparum; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Prospective Studies; Quinine; Stillbirth

The development of resistance by Plasmodium falciparum to anti-malarial drugs impedes any benefits of the drug. In addition, absence or delayed availability of current anti-malarial drugs in remote areas has the potential to results to parasite escape and continuous transmission.. The case of a 29-year old pregnant woman from Biase Local Government Area in Cross River State Nigeria presenting with febrile illness and high body temperature of 38.7 °C was reported. She looked pale and vomited twice on arrival at the health facility. Her blood smear on the first day of hospitalization was positive for P. falciparum by RDT, microscopy (21,960 parasite/µl) and real-time PCR, with a PCV of 18%. She was treated with 600 mg intravenous quinine in 500 ml of 5% Dextrose/0.9% Saline 8-hourly for 24 h. On the second day of hospitalization, she complained of weakness, persistent high-grade fever and vaginal bleeding. A bulging amnion from an extended cervix was observed. Following venous blood collection for laboratory investigations, 600 µg of misoprostol was inserted into the posterior fornix of her vagina as part of her obstetric care. Parenteral quinine was discontinued, and she was given full therapeutic regimen of artemether-lumefantrine 80/480 mg tablets to be taken for 3 days beginning from the second day. Her blood samples on the second and third day of hospitalization remained positive for P. falciparum by all three diagnostic methods. Single nucleotide polymorphism (SNP) assay on all three P. falciparum isolates revealed the presence of variants associated with multiple drug resistant markers.. Infecting P. falciparum isolates may have been resistant to initial quinine treatment resulting from parasite cross-resistance with other quinoline associated resistant markers such as 86Y and 184 F.. Therefore, the likely transmission of similarly resistant parasites in the study area calls for reinforcement of interventions and adherence to current World Health Organization guidelines in administering only approved drugs to individuals in order to mitigate parasite escape and eventual transmission to other susceptible individuals.

Topics: Abortion, Spontaneous; Adult; Africa, Western; Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Drug Resistance; Drug Resistance, Multiple; Female; Humans; Malaria; Malaria, Falciparum; Nigeria; Plasmodium falciparum; Pregnancy; Pregnant Women; Quinine