title: Revisiting doxycycline in pregnancy and early childhood--time to rebuild its reputation?
abstract: BACKGROUND
  Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood.
  
  
  METHODS
  A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found.
  
  
  CONCLUSIONS
  The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children.
authors.affiliation: a Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine , Mahidol University , Mae Sot , Tak , Thailand.
authors.forename: Ruby
authors.initials: R
authors.lastname: Cross
authors.affiliation: a Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine , Mahidol University , Mae Sot , Tak , Thailand.|b Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine , Mahidol University , Bangkok , Thailand.
authors.forename: Clare
authors.initials: C
authors.lastname: Ling
authors.affiliation: b Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine , Mahidol University , Bangkok , Thailand.|c Centre for Tropical Medicine & Global Health, Nuffield Department of Clinical Medicine , University of Oxford , Oxford , UK.
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.affiliation: a Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine , Mahidol University , Mae Sot , Tak , Thailand.|b Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine , Mahidol University , Bangkok , Thailand.|c Centre for Tropical Medicine & Global Health, Nuffield Department of Clinical Medicine , University of Oxford , Oxford , UK.
authors.forename: Rose
authors.initials: R
authors.lastname: McGready
authors.affiliation: b Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine , Mahidol University , Bangkok , Thailand.|c Centre for Tropical Medicine & Global Health, Nuffield Department of Clinical Medicine , University of Oxford , Oxford , UK.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Paris
mesh_terms: D000367:Age Factors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001424:Bacterial Infections / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D000075202:Contraindications; D004318:Doxycycline / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011256:Pregnancy Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline
keywords: Doxycycline; Orientia tsutsugamushi; Rickettsia typhi; major congenital anomalies; murine typhus; pregnancy; prenatal exposure; rickettsiosis; scrub typhus; side effects; teratogenicity; tetracycline; tooth discolouration; undifferentiated fever