Transplacental Effect of Tetracyclines on Teeth

Kline, Allen H.; Blattner, Russell J.; Lunin, M

doi:10.1001/jama.1964.03060280080021

Cited by 77 publications

(12 citation statements)

References 2 publications

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“…1/25 with slight spotted discoloration of upper incisors. [ 3 , 6 , 9 , 46 – 60 ] Reversible bone growth inhibition 25 0 NA NA # Mean fibula growth inhibition of up to 40% length during tetracycline treatment, rapid compensatory growth rate and return to normal upon discontinuation of drug. [ 61 ] Teratogenicity 16 214 56 1949 p = 0.001 (0.04; 0.07–0.75) Doxycycline: no evidence for increased teratogenicity observed, OR was equal to or smaller than controls.…”

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

162

117

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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.

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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

162

117

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“…Doxycycline can also inhibit the pro‐inflammatory effects of IL‐17 (Obradović et al, ). Tetracyclines share a linear fused tetracyclic nucleus and some tetracyclines (including the original tetracycline, referred to as tetracycline) not including doxycycline have been shown to cause dental staining in human neonates when administered during the second or third trimesters (Cohlan, ; Kline, Blattner, & Lunin, ; Toaff & Ravid, ). 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 et al, ; Gaillard et al, ) 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, ; Kazy, Puho, & Czeizel, ).…”

Section: Possible Implications For the Treatment Of Placental Malariamentioning

confidence: 99%

Genesis of placental sequestration in malaria and possible targets for drugs for placental malaria

Clark

2019

Birth Defects Research

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Malaria during pregnancy results in intrauterine growth restriction, fetal anemia, and infant mortality. Women are more susceptible to malaria during pregnancy due to malaria-induced inflammation and the sequestration of infected red blood cells in the placenta, which bind to the chondroitin sulfate portion of syndecan-1 on the syncytiotrophoblast and in the intervillous space. Syndecan-1 is a dimeric proteoglycan with an extracellular ectodomain that is cleaved from the transmembrane domain (referred to as "shedding") by matrix metalloproteinases (MMPs), likely the secreted MMP-9. The ectodomain includes four binding sites for chondroitin sulfate, which are proximal to the transmembrane domain, and six distal binding sites primarily for heparan sulfate. This "shedding" of syndecan-1 is inhibited by the presence of the heparan sulfate chains, which can be removed by heparanase. The intervillous space contains fibrin strands and syndecan-1 ectodomains free of heparan sulfate. The following is proposed as the sequence of events that leads to and is primarily responsible for sequestration in the intervillous space of the placenta. Inflammation associated with malaria triggers increased heparanase activity that degrades the heparan sulfate on the membrane-bound syndecan-1. Inflammation also upregulates MMP-9 and the removal of heparan sulfate gives MMP-9 access to cleave syndecan-1, thereby releasing dimeric syndecan-1 ectodomains with at least four chondroitin sulfate chains attached. These multivalent ectodomains bind infected RBCs together leading to their aggregation and entrapment in intervillous fibrin. This mechanism suggests possible new targets for anti-placental malaria drugs such as the inhibition of MMP-9. Doxycycline is an antimalarial drug which inhibits MMP-9. K E Y W O R D Sfibrin, heparanase, malaria, metalloproteinase, placenta, sequestration, syndecan-1

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“…The tetracyclines readily cross the placenta and are firmly bound by chelating to calcium in developing bone and tooth structures. 27 This produces brown discoloration of the teeth, hypoplasia of the enamel, inhibition of bone growth, 28 and other skeletal abnormalities. The yellowish-brown staining of the teeth usually occurs in the second or third trimesters of pregnancy after 24 weeks, whereas bone incorporation can occur earlier.…”

Section: Tetracyclinesmentioning

confidence: 99%

Antibiotics and Other Anti-infective Agents in Pregnancy and Lactation

Niebyl

2003

Am J Perinatol

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Serum levels of many drugs are lower in pregnancy compared with the nonpregnant state. Their renal clearance is higher and the maternal intravascular volume is expanded. Most antibiotics are safe for use in pregnancy and lactation. Tetracyclines cause fetal tooth discoloration and inhibition of bone growth if used in the second and third trimesters. Aminoglycosides carry a small risk of fetal ototoxicity. Quinolones may cause arthropathies in children, and so are currently not recommended for use in pregnancy. Most drugs are secreted into breast milk in very small amounts, not enough to have any therapeutic effect. The only antibiotics which may be of concern in nursing infants are sulfonamides and quinolones, and possibly metronidazole.

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Transplacental Effect of Tetracyclines on Teeth

Cited by 77 publications

References 2 publications

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

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

Genesis of placental sequestration in malaria and possible targets for drugs for placental malaria

Antibiotics and Other Anti-infective Agents in Pregnancy and Lactation

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