At least 45 Syrian refugees, including many children, have been killed in Aleppo after a regime artillery attack hit a group of displaced families trying to flee from rebel-held eastern areas of the city, according to the Syrian Civil Defence rescue organisation.

The Britain-based Syrian Observatory for Human Rights, a monitoring group, claimed it was the second time the Jub al-Quba neighborhood in eastern Aleppo was struck in as many days. An air strike killed 25 civilians on Tuesday. Thousands of east Aleppo residents have moved to Jub al-Quba and other such neighborhoods fleeing a government advance on the rebel-held east.

Also on Wednesday, Syrian state media said two children were among the eight killed in shelling on the city's governement western neighborhoods, which it blamed on the rebels.

The assault by Syrian forces comes amid warnings the city could witness one of the biggest massacres since the Second World War as President Assad's troops continue their offensive to re-take the city.

A sweeping advance by the Russian-backed Syrian army and allied militias has displaced thousands of people, leaving residents unsure where to turn to for safety as the frontline fighting rapidly moves and rebels struggle to maintain control of key neighbourhoods, the UN said on Tuesday.

Syrian Observatory chief Rami Abdurrahman said he predicts death tolls will spiral in east Aleppo as the internal displacement creates more residential density.

Since mid-November, more than 739 civilians have been killed and hundreds more injured in regime attacks on eastern Aleppo, according to figures released by local civil defense officials.

The Observatory said more than 50,000 out of an estimated quarter-million inhabitants have been displaced by attacks on rebel-held eastern Aleppo over the past four days. Many of them fled to safer ground in areas under government or Kurdish control. The International Committee of the Red Cross says around 20,000 people have fled.

The Observatory also claimed that the Syrian government had detained hundreds of people forced to flee the fighting. The Observatory said the government was detaining and questioning displaced people who have fled towards northeastern parts of the city. Some of the young men may be taken to join the army, while others may be investigated, it claimed, with more than 300 people missing.

A Syrian military source, talking to Reuters, denied anyone had been arrested but said the identities of people leaving rebel-held areas were being checked and that anyone who was unknown was being put in “specific places” in areas where civilians were gathered. The source said this was in case militants had left with them.

“A large amount of people came out,” the source said. “There are enormous numbers that need checking and follow-up. That's the situation.”