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Introduction to Drugs and Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Normal organogenesis and histogenesis during the embryonic development can be damaged outside the period of the embryo as a fetus. Traditionally, damage to a fetus not considered a teratogenic effect may present as a structural abnormality, but some authorities lump fetal effects into this category. Changes in cellular structures (e.g., brain cell arrangements during neuronal migration) occur during the fetal period. However, the predominant fetal event is hyperplastic growth (increase in cell number) with organs and other tissues becoming larger through cellular proliferation, and only secondarily through hypertrophy (increase in cell size). For example, the thyroid gland appears early in the fetal period, as does fetal endocrine function. Potential adverse effects during fetal development include maldevelopment due to interrupted cell migration and growth retardation (Jones, 1988). If blood flow to an organ or structure is interrupted or obstructed, structures that were normally formed during embryogenesis may become malformed during the fetal period (e.g., vascular disruption and fetal cocaine or warfarin exposure). The structure(s) deprived of blood flow necrose and are resorbed. A defect would result that may mimic an embryonic effect, but the true origin of the defect would be fetotoxicity.
Cardiac diseases in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Saravanan Kuppuswamy, Sudarshan Balla
All reported stenting during the acute phase of MI during pregnancy were performed with bare metal stents. The safety of drug-eluting stents in pregnant woman is therefore still unknown. Because drug-eluting stents require prolonged antiplatelet therapy with aspirin and thienopyridine, and the incidence of cesarean section deliveries in patients with heart disease is relatively high, the use of drug-eluting stent during pregnancy should be avoided if possible. Although animal experiments do not demonstrate teratogenic effect, there are no studies in pregnant women and should be used in pregnancy only if clearly needed.
Alternative Methodologies to Animal Testing
Published in Nicola Loprieno, Alternative Methodologies for the Safety Evaluation of Chemicals in the Cosmetic Industry, 2019
In whole animals the teratogenic effect is represented by any kind of malformations (morphological and functional) occurring in the embryo; the target, however, is not only the embryo, but also the fetus, the placenta, and the mother. This situation complicates the development of a unique in vitro test for teratogens: the knowledge of the mechanism by which a class of chemicals produces teratogenic effects may influence the choice of the in vitro test system.
Retinoic acid as a teratogen: IX-Induction of fetal skeletal anomalies and alteration in the utero-placental expression pattern of EGFR during mice development
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Ahmed Said, Abdel-Rahman S. Sultan, Reda A. Ali, Mohsen A. Moustafa
The fetal skeletons from maternal RA treated groups revealed incomplete ossification and non-ossified different parts, the skeletal anomalies mostly appeared as incomplete ossification of the frontal, parietal, and interparietal, occipital condyles agenesis, caudal vertebrae agenesis, scapula and humerus hypoplasia, radius, ulna, carpus, meta carpus agenesis, femur hypoplasia, tibia, fibula, tarsus, meta tarsus agenesis, pelvic hypoplasia. As shown previously, the skeletal examination of the diaphanized fetuses showed bone changes, especially of the forelimbs, hindlimbs, pelvic hypoplasia, and tail agenesis in mice [38] and chick [7,8]. Next, the morphological malformations and skeletal anomalies of the fetuses from RA treated groups permitted us to investigate the mechanism of RA teratogenic effect, either through the placental abnormality or direct effect on the fetus.
Genotoxic and mutagenic studies of teratogens in developing rat and mouse
Published in Drug and Chemical Toxicology, 2019
Eyyüp Rencüzoğulları, Muhsin Aydın
As a result, chemicals can cause teratogenic effects by initiating mutations. These can be referred as genotoxic or mutagenic chemicals. However, some chemicals may have teratogenic effect without displaying any genotoxic effect. These are referred as nongenotoxic or nonmutagenic teratogens. However, it should be noted that the most sensitive period of the pregnancy is the first trimester period. During this period, it is important to stay away from all kinds of chemicals unless it is recommended by a professional. Additionally, it is also known that chemicals may have different teratogenic effects when taken at different stages of gestation. Doses and exposure times of the chemicals during pregnancy are extremely important for teratogenicity. For healthy generations, it is recommended that people should take the given information into consideration and must not use any medication without doctor's advice during pregnancy.
Phenylketonuria in the adult patient
Published in Expert Opinion on Orphan Drugs, 2019
Leticia Ceberio, Álvaro Hermida, Eva Venegas, Francisco Arrieta, Montserrat Morales, Maria Forga, Montserrat Gonzalo
As it is described in the diagnosis section, Mpku is caused by the exposure of the fetus to high levels of Phe (above 360 µmol/L). Its teratogenic effect can result in growth retardation, microcephaly, intellectual disabilities and CHD [37]. The prenatal-exposure effects show a dose-response relation, with higher levels of exposure leading to higher levels of disability [91]. Therefore, women of childbearing age require especially intensive management [92] (Table 2), through a restricted dietary and/or pharmacologic treatment that maintains the phenylalaninemia within the range of 120–360 µmol/L and thereby allows a normal fetus development without potential teratogenic complications [93,94]. Before women conceive, it is recommended to achieve and maintain a stable optimal range of blood Phe levels for a minimum of 2 weeks [4]. At least weekly monitoring of blood Phe concentrations, before and throughout the pregnancy, is recommended, except in individualized cases including twin pregnancies that may require daily monitoring [4,56]. Additionally, a supplement of 400 µg of folic acid should be given to all women considering pregnancy and for the first 12 weeks of pregnancy, irrespective of the folic acid content of the Phe-free L-amino acid formulas [4].