Effect of doxycycline treatment during pregnancy for birth outcomes

Kazy, Zoltán; Puhó, Erzsébet; Czeizel, Andr̀ew E.

doi:10.1016/j.reprotox.2007.07.011

Cited by 15 publications

(8 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Doxycycline is inexpensive and the drug of choice in non-pregnant patients for rickettsial illness and the shortest described treatment course is at least 3 days as well as having short fever clearance times [45] . Doxycycline can be used in pregnancy, if no alternative is available and there is no other contraindication [46] , which is a real case scenario in much of the rural tropics, in addition to it being a cheaper alternative than azithromycin. Most treatment efficacy studies of typhus have been limited to a short follow-up of 28 days but like malaria [47] a longer duration of follow-up is likely to be required to monitor for relapse in pregnant women and further pharmacokinetic studies are required [48] .…”

Section: Discussionmentioning

confidence: 99%

Pregnancy Outcome in Relation to Treatment of Murine Typhus and Scrub Typhus Infection: A Fever Cohort and a Case Series Analysis

et al. 2014

View full text Add to dashboard Cite

BackgroundThere is a paucity of published reports on pregnancy outcome following scrub and murine typhus despite these infections being leading causes of undifferentiated fever in Asia. This study aimed to relate pregnancy outcome with treatment of typhus.Methodology/Principal FindingsData were analyzed from: i) pregnant women with a diagnosis of scrub and/or murine typhus from a fever cohort studies; ii) case series of published studies in PubMed using the search terms “scrub typhus” (ST), “murine typhus” (MT), “Orientia tsutsugamushi”, “Rickettsia tsutsugamushi”, “Rickettsia typhi”, “rickettsiae”, “typhus”, or “rickettsiosis”; and “pregnancy”, until February 2014 and iii) an unpublished case series. Fever clearance time (FCT) and pregnancy outcome (miscarriage and delivery) were compared to treatment. Poor neonatal outcome was a composite measure for pregnancies sustained to 28 weeks or more of gestation ending in stillbirth, preterm birth, or delivery of a growth restricted or low birth weight newborn.ResultsThere were 26 women in the fever cohort. MT and ST were clinically indistinguishable apart from two ST patients with eschars. FCTs (median [range] hours) were 25 [16–42] for azithromycin (n = 5), 34 [20–53] for antimalarials (n = 5) and 92 [6–260] for other antibiotics/supportive therapy (n = 16). There were 36.4% (8/22) with a poor neonatal outcome.In 18 years, 97 pregnancies were collated, 82 with known outcomes, including two maternal deaths. Proportions of miscarriage 17.3% (14/81) and poor neonatal outcomes 41.8% (28/67) were high, increasing with longer FCTs (p = 0.050, linear trend). Use of azithromycin was not significantly associated with improved neonatal outcomes (p = 0.610)ConclusionThe published ST and MT world literature amounts to less than 100 pregnancies due to under recognition and under diagnosis. Evidence supporting the most commonly used treatment, azithromycin, is weak. Collaborative, prospective clinical trials in pregnant women are urgently required to reduce the burden of adverse maternal and newborn outcomes and to determine the safety and efficacy of antimicrobial treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Pregnancy Outcome in Relation to Treatment of Murine Typhus and Scrub Typhus Infection: A Fever Cohort and a Case Series Analysis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Treatment during the first and second trimesters of pregnancy resulted in longer gestational age at delivery and a reduction in the rate of preterm births (based on three births); and mild intrauterine fetal growth retardation in five births between the thirty-first and thirty-fourth gestational week, however this did not contraindicate doxycycline use. [ 105 ] Since the reduced use of doxycycline is a consequence of the ‘tetracycline class effect’ based on fear of, but no evidence for tooth-staining and bone growth impediment, re-consideration of adequate clinical evaluation of doxycycline seems sensible. Although the US FDA states that the risk of an association with tooth staining cannot be eliminated due to the insufficient availability of supporting data, it is likely to be minimal.…”

Section: Resultsmentioning

confidence: 99%

Revisiting doxycycline in pregnancy and early childhood – time to rebuild its reputation?

Cross

Ling

Day

et al. 2016

Expert Opinion on Drug Safety

170

109

View full text Add to dashboard Cite

Introduction: 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. Areas Covered: 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. Expert Opinion: 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.

show abstract

“…The dNOELs in mice and rabbits were 20 and 50 mg/kg/day resulting in HED ratios (relative to the treatment dose) for mice and rabbits of 0.4 and 4.0, respectively. Initially contraindicated for use in pregnancy because of a possible tetracycline class effect, recent reviews have found little evidence to suggest an adverse effect of doxycycline on pregnancy (Cross, Ling, Day, McGready, & Paris, 2016; Gaillard, Madamet, & Pradines, 2015) and doxycycline use during the first and second trimesters to combat various infections other than malaria has had positive effects on pregnancy outcome (Gaillard et al, 2018; Kazy, Puhó, & Czeizel, 2007).…”

Section: Non‐artemisinin Antimalarial Drugs In Pregnancymentioning

confidence: 99%

Teratogen update: Malaria in pregnancy and the use of antimalarial drugs in the first trimester

Clark

2020

Birth Defects Research

View full text Add to dashboard Cite

Malaria is a particular problem in pregnancy because of enhanced sensitivity, the possibility of placental malaria, and adverse effects on pregnancy outcome. Artemisinin-containing combination therapies (ACTs) are the most effective antimalarials known. WHO recommends 7-day quinine therapy for uncomplicated Plasmodium falciparum malaria in the first trimester despite the superior tolerability and efficacy of 3-day ACT regimens because artemisinins caused embryolethality and/or cardiovascular malformations at relatively low doses in rats, rabbits, and monkeys. The developmental toxicity of artesunate, artemether, and DHA were similar in rats but artesunate was embryotoxic at lower doses in rabbits (5 mg/kg/day) than artemether (no effect level = 25 mg/kg/day). In clinical studies in Africa, treatment with artemether-lumefantrine in the first trimester was observed to be highly efficacious and the miscarriage rate (≤3.1%) was similar to no antimalarial treatment (2.6%). When data from the first-trimester use of largely artesunate-based therapies in Thailand were pooled together, there was no difference in miscarriage rate compared to quinine. However, individually, artesunate-mefloquine was associated with a higher miscarriage rate (15/ 71 = 21%) compared to other artemisinin-based therapies including 7-day artesunate + clindamycin (2/50 = 4%) and quinine (92/842 = 11%). Thus, appropriate statistical comparisons of individual ACT groups are needed prior to assuming that they all have the same risk for developmental toxicity. Current limitations in the assessment of the safety of ACTs in the first trimester are a lack of exposures early in gestation (gestational weeks 6-7), limited postnatal evaluation for cardiovascular malformations, and the pooling of all ACTs for the assessment of risk.

show abstract

Effect of doxycycline treatment during pregnancy for birth outcomes

Cited by 15 publications

References 3 publications

Pregnancy Outcome in Relation to Treatment of Murine Typhus and Scrub Typhus Infection: A Fever Cohort and a Case Series Analysis

Pregnancy Outcome in Relation to Treatment of Murine Typhus and Scrub Typhus Infection: A Fever Cohort and a Case Series Analysis

Revisiting doxycycline in pregnancy and early childhood – time to rebuild its reputation?

Teratogen update: Malaria in pregnancy and the use of antimalarial drugs in the first trimester

Contact Info

Product

Resources

About