Just got back from a trip with wife and 20 mo old twins - we had two SQ C seats (lots and lots of space - no problem) as well as two BF intl seats on UA/CO on domestic connection (much tighter space but still manageable when fully reclined as flat bed). Aside from takeoffs and landings we did not have to hold them at all.
Kids mostly behaved and we were able to have proper meals while they were napping and things went reasonably well. This time Benadryl worked on one but not the other perhaps because we gave a very small dose.

Both on SQ and UA we were allowed to have a pair of adjacent seats - apparently oxygen masks were not an issue there.

As a comparison a few months earlier we had four miserably tight Y seats on NH and it was a far more uncomfortable and tiring experience for us even though both kids slept better perhaps due to flight times and better Benadryl response.

Have SQ C and CX F coming up before they turn two...