CSS can create accessibility issues a few ways:
- Hiding content with display:none when it needs to remain available to assistive tech (there are various accessible "visually hidden" tricks which can be used instead). Note that display:none is still the correct way to hide content that should be hidden from all humans.
- Using generated content, eg. icon fonts, where the content is confusing (random letters used to display an icon font glyph)
- Changing the display order of content into something confusing. This is where flexbox and grid can really cause some issues.
- Suppressing visual focus indicators, eg. removing the default dotted boxes or outlines on the currently-focused element, so keyboard users can't see where tehy are on the page.
- CSS also controls the colours in the page, so most colour issues come from CSS. That includes poor contrast, poor combinations of colour, meaning indicated only with colour, opacity reducing the opacity of accessible base colours and so on.
So yes the new layout systems can cause accessibility issues; the answer in the end is to ensure you test the tab order is still logical, content still available to assistive tech and so on.