With my oldest son, I can't really say what was the biggest since it all happened at once and the combination was so incredibly overwhelming it's impossible to separate one thing from another. My son was teething at birth and he had colic, so he screamed 18 hours per day for the first 6 months. I also started chemo when he was 6 weeks old and had a 2 yr. battle to become cancer free.
With my daughter, everything was easy. Basically, keeping the cats out of her crib was the biggest challenge I had.
With my youngest, it was the time we were in the hospital after he was born. He was in the hospital for 6 days, the last 2 days in the NICU. We had a lot of issues and I could write a book about everything that happened....some turned out good, some was horrible and has had lasting impacts.
We my last child when she was it was trying to take care of my two older kids during my lo's growth spurt.. I can't walk around and nurse like some can . So it made it very difficult to tend to my older two girls.
With my first it was nursing because we had trouble with the latching. With my second it was probably sleep deprivation since my first was still waking up during the night too. With this new little one there hasn't really been a challenge yet but my husband is still on paternity leave so that's probably why. Lol!