Talk:Abnormal Development - Teratogens

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Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Teratogens. Retrieved February 22, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Abnormal_Development_-_Teratogens

2014

Dispensing of potentially teratogenic drugs before conception and during pregnancy: a population-based study

BJOG. 2014 Oct 15. doi: 10.1111/1471-0528.13128. [Epub ahead of print]

Zomerdijk I1, Ruiter R, Houweling L, Herings R, Straus S, Stricker B.

Abstract

OBJECTIVE: To study the dispensing of potentially teratogenic drugs in the 12-month period before as well as during pregnancy in the Netherlands. DESIGN: Population-based study. SETTING: A cohort was constructed using a linkage between the PHARMO Database Network and the Netherlands Perinatal Registry (PRN). POPULATION: A total of 203 962 Dutch pregnancies reported between 1999 and 2007 METHODS: Drug-dispensing information was identified from the PHARMO Database Network for the 12-month period before conception and during pregnancy. Drugs with either a Swedish FASS 'D' classification, an Australian ADEC or American FDA 'D' or 'X' classification were considered potentially teratogenic (n = 202). MEAN OUTCOME MEASURES: Proportion of pregnancies that received potentially teratogenic drugs in the 12-month period before and during pregnancy and specific for the risk category X drugs and newly initiated drugs. RESULTS: Sixteen percent of the pregnancies received a potentially teratogenic drug in the 12-month period before and 5.07% during pregnancy. Doxycycline and paroxetine were most frequently received during pregnancy by 1.01% and 0.85% of women, respectively; 0.66% of the women received a risk category X drug during pregnancy which most frequently consisted of triptorelin (0.25%), norethisterone (0.22%) and simvastatin (0.03%). Fifty-three percent of the women who received a potentially teratogenic drug during pregnancy received this for the first time during the study period. These percentages were heterogeneous between therapeutic drug classes. CONCLUSIONS: Five percent of the pregnancies received a potentially teratogenic drug during pregnancy and 0.66% received a drug from the risk category X. It may be possible to reduce these proportions when reasons for prescription have been explored. © 2014 Royal College of Obstetricians and Gynaecologists. KEYWORDS: Drug safety; embryotoxic; maternal drug use; pregnancy; teratogens

PMID 25316196

2012

Assessment of gross fetal malformations: the modernized Wilson technique and skeletal staining

Methods Mol Biol. 2012;889:451-63.

Seegmiller RE, Cook N, Goodwin K, Leishman T. Source School of Dental Medicine, Roseman University, South Jordan, UT, USA. robert_seegmiller@byu.edu

Abstract

Teratology is the study of anatomical and physiological abnormalities, commonly known as birth defects. If an embryo is exposed to a harmful substance, or teratogen, during the critical period of development, an ensuing malformation may occur. These malformations and their associated mechanisms are studied and analyzed in laboratory animals in order to prevent them from occurring in humans. Rodents, such as rabbits, rats, and mice, have commonly been used in such studies because of their similarity to humans. In 1959, James G. Wilson designed, developed, and tested a protocol on how to observe and analyze structural malformations in rodent fetuses, which included external examination, skeletal evaluation, soft tissue analysis, and data collection/analysis. Although many years have passed since Wilson created this protocol, it is still widely used to this day, and only minor changes have been made to his instructions such as the chemicals used in the experiments and also the analysis of the experimental data. While only minor modifications have been made to this protocol since its beginning, major advances have been made in the dissemination of teratology information to the public such that information is now available through the Internet--information including the identification of an increasing number of teratogens and the understanding of the pathogenesis as it relates to the etiology of birth defects. Despite these advances, however, there has been little decrease in the overall incidence of major birth defects, although significantly improved reporting and ascertainment of birth defects must be factored into the equation in determining birth defect rates. Future birth defect prevention may be based on the understanding of individual genomes and pharmacogenomics, and as the interaction between teratogenic and genetic factors is better understood--with the hope that the incidence of both chemically induced and genetic defects will one day be substantially reduced.

PMID 22669682

2011

Maternal exposure to multi-wall carbon nanotubes does not induce embryo-fetal developmental toxicity in rats

Birth Defects Res B Dev Reprod Toxicol. 2011 Feb;92(1):69-76. doi: 10.1002/bdrb.20283. Epub 2011 Jan 19.

Lim JH, Kim SH, Shin IS, Park NH, Moon C, Kang SS, Kim SH, Park SC, Kim JC.

College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea. Abstract BACKGROUND: Although the potential risk of carbon nanotubes (CNTs) to humans has recently increased due to expanding production and widespread use, the potential adverse effects of CNTs on embryo-fetal development have not yet been determined.

METHODS: This study investigated the potential effects of multi-wall CNTs (MWCNTs) on pregnant dams and embryo-fetal development in rats. MWCNTs were administered to pregnant rats by gavage at 0, 40, 200, and 1,000 mg/kg/day. All dams were subjected to Cesarean section on day 20 of gestation, and the fetuses were examined for any morphological abnormalities.

RESULTS: All animals survived to the end of the study. A decrease in thymus weight was observed in the high dose group in a dose-dependent manner. However, maternal body weight, food consumption, and oxidant-antioxidant balance in the liver were not affected by treatment with MWCNTs. No treatment-related differences in gestation index, fetal deaths, fetal and placental weights, or sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in incidences of abnormalities between the groups.

CONCLUSIONS: The results show that repeated oral doses of MWCNTs during pregnancy induces minimal maternal toxicity and no embryo-fetal toxicity at 1,000 mg/kg/day in rats. The no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1,000 mg/kg/day for embryo-fetal development. In this study, the dosing formulation was not analyzed to determine the degree of reaggregation (or not), nor were blood levels of CNT's measured in the dosed animals to verify or characterize absorption. Birth Defects Res (Part B) 92:69-76, 2011.  © 2011 Wiley-Liss, Inc.

© 2011 Wiley-Liss, Inc. PMID: 21254368