A bias assessment plot for the outcome of congenital malformations is shown in Figure 7.
Although no adverse effects of the transfer of cryopreserved embryos on IVF outcomes, including malformations, were shown in two European registry studies (Kallen et al., 2005; Pinborg et al., 2008), more high-quality studies are required to assess long-term safety, given the recent and rapid development of cryopreservation techniques (Shaw et al., 1991).
Freezing lesions to the developing cortical plate of rodents results in a focal malformation resembling human 4-layered microgyria, and this malformation has been shown to result in local and widespread disruptions of neuronal architecture, connectivity, and physiology.
Patients with a heterozygous mutation of CCM3 have a high susceptibility to develop cerebral cavernous malformations, and it has been shown recently that they can also develop meningiomas, which places CCM3 as a possible tumor suppressor gene (Clark et al., 2013; Riant et al., 2013).
The incidences of external, visceral and skeletal malformations as well as total malformations are also shown in Table A9.
The iAs-induced malformations in mouse have also been shown to be associated with systems-level changes in gene expression (Robinson et al. 2011).
If the mothers were not able to bring their children for some reason, they were shown pictures of malformations and asked to indicate if their child had those malformations.
During the interview, pictorials of major congenital malformations and, low birth weight babies were shown to aid recall.
Recently, exposure to 17β-estradiol and octylphenol has been shown to cause malformations in embryos of viviparous eelpout at fairly high – but still environmentally realistic concentrations [ 16].
21 Methotrexate, a common RA treatment, can be damaging to fetal development (at least at high doses) 22 23 while other disease-modifying antirheumatic drugs such as leflunomide have been shown to cause malformations in animal studies.
