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In one of the observational studies, in which 39 pregnant women were included after assessing their cotinine, the nicotine metabolite and the genes RELN , PLP1 , MBP and BDNF , down-regulation was observed in samples collected from umbilical blood and, since those genes control brain growth, it might be stated that tobacco smoke can by one of the causes of impaired neurological development and that it impacts fetal brain programming [15]

Since 1907, Bhutan had been ruled by a lineage of progressive monarchs