{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T07:31:24Z","timestamp":1775028684023,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Danish Council for Strategic Research, Innovationsfonden Denmark","award":["1309-00003B"],"award-info":[{"award-number":["1309-00003B"]}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R209-2015-3580"],"award-info":[{"award-number":["R209-2015-3580"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps, particularly the sextuple mutant haplotype threatens the antimalarial effectiveness of sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment during pregnancy (IPTp). To explore the impact of sextuple mutant haplotype infections on outcome measures after provision of IPTp with SP, we monitored birth outcomes in women followed up from before conception or from the first trimester until delivery. Women infected with sextuple haplotypes, in the early second trimester specifically, delivered newborns with a lower birth weight compared with women who did not have malaria during pregnancy (difference, \u2212267 g; 95% confidence interval, \u2212454 to \u221259; P\u2005=\u2005.01) and women infected with less SP-resistant haplotypes (\u2212461 g; \u2212877 to \u221244; P\u2005=\u2005.03). Thus, sextuple haplotype infections seem to affect the effectiveness of SP for IPTp and directly affect birth outcome by lowering birth weight. Close monitoring and targeted malaria control during early pregnancy is therefore crucial to improving birth outcomes.<\/jats:p>","DOI":"10.1093\/infdis\/jiab117","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T12:11:30Z","timestamp":1614341490000},"page":"1605-1613","source":"Crossref","is-referenced-by-count":10,"title":["Reduced Birth Weight Caused by Sextuple Drug-Resistant <i>Plasmodium falciparum<\/i> Infection in Early Second Trimester"],"prefix":"10.1093","volume":"224","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6484-1165","authenticated-orcid":false,"given":"Helle","family":"Hansson","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel T R","family":"Minja","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofie L","family":"Moeller","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P A","family":"Lusingu","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ib C","family":"Bygbjerg","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Mathilde","family":"Yde","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus W","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidsel","family":"Nag","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omari A","family":"Msemo","sequence":"additional","affiliation":[{"name":"National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thor G","family":"Theander","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Alifrangis","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christentze","family":"Schmiegelow","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"2021111805071715800_CIT0001","author":"World Health Organization"},{"key":"2021111805071715800_CIT0002","doi-asserted-by":"crossref","first-page":"e1101","DOI":"10.1016\/S2214-109X(17)30340-6","article-title":"Quantification of the association between malaria in pregnancy and stillbirth: a systematic review and meta-analysis","volume":"5","author":"Moore","year":"2017","journal-title":"Lancet Glob Health"},{"key":"2021111805071715800_CIT0003","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S1473-3099(07)70021-X","article-title":"Epidemiology and burden of malaria in pregnancy","volume":"7","author":"Desai","year":"2007","journal-title":"Lancet Infect Dis"},{"key":"2021111805071715800_CIT0004","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0140-6736(13)60993-9","article-title":"Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis","volume":"382","author":"Katz","year":"2013","journal-title":"Lancet"},{"key":"2021111805071715800_CIT0005","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1007\/s00125-012-2589-y","article-title":"The thrifty phenotype hypothesis revisited","volume":"55","author":"Vaag","year":"2012","journal-title":"Diabetologia"},{"key":"2021111805071715800_CIT0006","doi-asserted-by":"crossref","first-page":"214","DOI":"10.4269\/ajtmh.2011.11-0103","article-title":"Influence of the timing of malaria infection during pregnancy on birth weight and on maternal anemia in Benin","volume":"85","author":"Huynh","year":"2011","journal-title":"Am J Trop Med Hyg"},{"key":"2021111805071715800_CIT0007","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1473-3099(11)70339-5","article-title":"Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study","volume":"12","author":"McGready","year":"2012","journal-title":"Lancet Infect Dis"},{"key":"2021111805071715800_CIT0008","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1475-2875-11-71","article-title":"An analysis of timing and frequency of malaria infection during pregnancy in relation to the risk of low birth weight, anaemia and perinatal mortality in Burkina Faso","volume":"11","author":"Valea","year":"2012","journal-title":"Malar J"},{"key":"2021111805071715800_CIT0009","doi-asserted-by":"crossref","first-page":"e53794","DOI":"10.1371\/journal.pone.0053794","article-title":"Malaria and fetal growth alterations in the 3(rd) trimester of pregnancy: a longitudinal ultrasound study","volume":"8","author":"Schmiegelow","year":"2013","journal-title":"PLoS One"},{"key":"2021111805071715800_CIT0010","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/infdis\/jiy735","article-title":"Malaria in early pregnancy and the development of the placental vasculature","volume":"220","author":"Moeller","year":"2019","journal-title":"J Infect Dis"},{"key":"2021111805071715800_CIT0011","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1093\/infdis\/jix530","article-title":"Plasmodium falciparum infection early in pregnancy has profound consequences for fetal growth","volume":"216","author":"Schmiegelow","year":"2017","journal-title":"J Infect Dis"},{"key":"2021111805071715800_CIT0012","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.3201\/eid1909.130133","article-title":"Plasmodium falciparum mutant haplotype infection during pregnancy associated with reduced birthweight, Tanzania","volume":"19","author":"Minja","year":"2013","journal-title":"Emerg Infect Dis"},{"key":"2021111805071715800_CIT0013","volume-title":"Guidelines for the treatment of malaria","author":"World Health Organization","year":"2015","edition":"3"},{"key":"2021111805071715800_CIT0014","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/S1473-3099(18)30732-1","article-title":"Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis","volume":"19","author":"van Eijk","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2021111805071715800_CIT0015","doi-asserted-by":"crossref","first-page":"e9438","DOI":"10.1371\/journal.pone.0009438","article-title":"Malaria prevention with IPTp during pregnancy reduces neonatal mortality","volume":"5","author":"Men\u00e9ndez","year":"2010","journal-title":"PLoS ONE"},{"key":"2021111805071715800_CIT0016","doi-asserted-by":"crossref","first-page":"e942","DOI":"10.1016\/S2214-109X(20)30119-4","article-title":"Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysis","volume":"8","author":"Roh","year":"2020","journal-title":"Lancet Glob Health"},{"key":"2021111805071715800_CIT0017","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/0169-4758(89)90257-3","article-title":"Point mutations and pyrimethamine resistance in Plasmodium falciparum","volume":"5","author":"Hyde","year":"1989","journal-title":"Parasitol Today"},{"key":"2021111805071715800_CIT0018","doi-asserted-by":"crossref","first-page":"13944","DOI":"10.1073\/pnas.94.25.13944","article-title":"Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum","volume":"94","author":"Triglia","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021111805071715800_CIT0019"},{"key":"2021111805071715800_CIT0020","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/cid\/civ881","article-title":"Impact of sulfadoxine-pyrimethamine resistance on effectiveness of intermittent preventive therapy for malaria in pregnancy at clearing infections and preventing low birth weight","volume":"62","author":"Desai","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2021111805071715800_CIT0021","doi-asserted-by":"crossref","first-page":"9027","DOI":"10.1073\/pnas.0901415106","article-title":"Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment","volume":"106","author":"Harrington","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021111805071715800_CIT0022","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/infdis\/jiaa145","article-title":"Interactions between antenatal sulfadoxine-pyrimethamine, drug-resistant Plasmodium falciparum parasites and delivery outcomes in Malawi","volume":"222","author":"Taylor","year":"2020","journal-title":"J Infect Dis"},{"key":"2021111805071715800_CIT0023","doi-asserted-by":"crossref","first-page":"e024861","DOI":"10.1136\/bmjopen-2018-024861","article-title":"FOETAL for NCD-FOetal exposure and epidemiological transitions: the role of anaemia in early life for non-communicable diseases in later life: a prospective preconception study in rural Tanzania","volume":"9","author":"Hjort","year":"2019","journal-title":"BMJ Open"},{"key":"2021111805071715800_CIT0024","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12887-019-1500-0","article-title":"Anthropometric measurements can identify small for gestational age newborns: a cohort study in rural Tanzania","volume":"19","author":"Paulsen","year":"2019","journal-title":"BMC Pediatr"},{"key":"2021111805071715800_CIT0025","doi-asserted-by":"crossref","first-page":"335","DOI":"10.4269\/ajtmh.16-0700","article-title":"Molecular evidence of malaria and zoonotic diseases among rapid diagnostic test-negative febrile patients in low-transmission season, Mali","volume":"96","author":"Tour\u00e9","year":"2017","journal-title":"Am J Trop Med Hyg"},{"key":"2021111805071715800_CIT0026","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s12936-019-2894-8","article-title":"Proof of concept: used malaria rapid diagnostic tests applied for parallel sequencing for surveillance of molecular markers of anti-malarial resistance in Bissau, Guinea-Bissau during 2014\u20132017","volume":"18","author":"Nag","year":"2019","journal-title":"Malaria J"},{"key":"2021111805071715800_CIT0027","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0035-9203(99)90120-7","article-title":"Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand","volume":"93","author":"Snounou","year":"1999","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2021111805071715800_CIT0028","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.trstmh.2010.01.013","article-title":"The effect of timing and frequency of Plasmodium falciparum infection during pregnancy on the risk of low birth weight and maternal anemia","volume":"104","author":"Kalilani","year":"2010","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2021111805071715800_CIT0029","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1365-3016.2010.01181.x","article-title":"Reliability of routine clinical measurements of neonatal circumferences and research measurements of neonatal skinfold thicknesses: findings from the Born in Bradford study","volume":"25","author":"West","year":"2011","journal-title":"Paediatr Perinat Epidemiol"},{"key":"2021111805071715800_CIT0030","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/1475-2875-11-319","article-title":"Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study","volume":"11","author":"Griffin","year":"2012","journal-title":"Malar J"},{"key":"2021111805071715800_CIT0031","doi-asserted-by":"crossref","first-page":"e0003824","DOI":"10.1371\/journal.pntd.0003824","article-title":"Malaria in pregnancy interacts with and alters the angiogenic profiles of the placenta","volume":"9","author":"Ata\u00edde","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"2021111805071715800_CIT0032","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.placenta.2003.10.009","article-title":"Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy","volume":"25","author":"Kaufmann","year":"2004","journal-title":"Placenta"},{"key":"2021111805071715800_CIT0033","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1093\/infdis\/jiy009","article-title":"Prevalence and associated risk factors of malaria in the first trimester of pregnancy: a preconceptional cohort study in Benin","volume":"217","author":"Accrombessi","year":"2018","journal-title":"J Infect Dis"},{"key":"2021111805071715800_CIT0034","author":"Ministry of Health Community Development, Gender, Elderly and Children (Tanzania Mainland), Ministry of Health (Zanzibar), National Bureau of Statistics, Office of the Chief Government Statistician (Zanzibar), and ICF","year":"2016"},{"key":"2021111805071715800_CIT0035","doi-asserted-by":"crossref","first-page":"e871","DOI":"10.1016\/S2214-109X(20)30216-3","article-title":"Defining the combined benefit of intermittent preventive malaria treatment in pregnancy","volume":"8","author":"Salman","year":"2020","journal-title":"Lancet Glob Health"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiab117\/39650803\/jiab117.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/224\/9\/1605\/41159921\/jiab117.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/224\/9\/1605\/41159921\/jiab117.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T07:40:09Z","timestamp":1637221209000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/224\/9\/1605\/6158222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,3]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,3,3]]},"published-print":{"date-parts":[[2021,11,16]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiab117","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2021,3,3]]}}}