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Mr Twyford has been under constant pressure over the troubled KiwiBuild programme. The plan to build 100,000 affordable homes over 10 years has been scaled back and the deadlines pushed out.
"In the housing area, what we are trying to do here, our ambition in addressing the housing crisis hasn't been done before, and so it hasn't been an easy area of work," Ms Ardern told Morning Report.
"So I'm loathe to see one individual carry any blame for what has been a policy that's been difficult - but we don't give up on the ambition around. So I will be a bit defensive there."
She dismissed criticism of Mr Twyford's non-attendance at a KiwiBuild conference, saying it wasn't possible when he had papers before Cabinet that day, so departmental officials went instead.
"I don't think attendance at a conference deserves quite the amount of coverage it's been receiving."
Commenting on new US sanctions on Iran, Ms Ardern said New Zealand was calling for de-escalation of tensions.
The US has imposed new sanctions targeting Iranian Supreme Leader Ayatollah Ali Khamenei and other senior Iranian officials.
President Donald Trump said the sanctions were in part a response to last week's downing of a US drone by Iran, but "would have happened anyway" and would deny the senior leadership access to key financial resources and support.
New Zealand, like the rest of the international community, remained committed to Iran nuclear deal, Ms Arden said.
New Zealand had spoken out about Iran's announcement it planned to breach the limit on its stockpile of enriched uranium was set under the 2015 nuclear deal with world powers, but was equally calling for de-escalation.
"No-one wants to see this continue to escalate - it's in no-one's interest.
"Our preference of course had been to maintain the Iran nuclear deal - that puts us alongside members of the EU."
New Zealand was making its own assessments of the US view that Iran was responsible for bombing of oil tankers, which was the usual process. "We do make our own assessments of evidence and that informs our decisions."
Ms Ardern declined to comment on whether Sir John Key had a conflict of interest, as both ANZ New Zealand board chair and a member of the bank's Australian board, as suggested by Deputy Prime Minister Winson Peters yesterday.
Ms Ardern said Mr Peters was "absolutely entitled" to take his position. "These are just calls that we each individually made, I'm taking my position and the deputy prime minster is entitled to his."
She pointed to reviews announced yesterday including into whether the Reserve Bank had the powers it needed on bank leaders' conduct and expectations.