Forces loyal to President Bashar Al Assad have taken over more than half of rebel-held Eastern Ghouta, splitting the remainder into three pockets and segregating Douma from the rest of the enclave.
The regime's advances have dealt another setback to rebel fighters and threatens to exacerbate an already dire humanitarian situation.
More than 1,000 civilians have been killed in the Syrian regime’s 20-day Russian-backed air campaign and ground offensive to capture the last rebel bastion on the capital's doorstep.
On Saturday, regime forces isolated Ghouta’s main town of Douma and cut off a road linking it to the town of Harasta further west, according to the UK-based Syrian Observatory for Human Rights.
"Regime forces have therefore divided Eastern Ghota into three parts – Douma and its surroundings, Harasta in the west and the rest of the towns further south," said the Observatory.
It said the death toll had reached 1,031 civilians, including 219 children. More than 4,350 have been injured.
They include dozens of decomposing bodies still trapped under pulverised residential blocks in the towns of Hammuriyeh, Saqba, and Misraba.
On Saturday, at least 20 civilians, including four children, were killed in Douma. Also, 17 civilians were killed in other battlefront towns, said the monitor group.
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On Sunday, government troops battered the edges of each pocket with air raids, barrel bombs, and rockets, said the Observatory.
Residents have been crowding into basements in towns across the enclave to shelter from the ferocious and indiscriminate bombardment. The international medical charity Doctors Without Borders said 15 of the 20 hospitals and clinics it supports have been damaged.
According to the Russian military more than 50 civilians were evacuated from the besieged suburbs of Damascus on Sunday.
"Today, 52 civilians, including 26 children, were brought from eastern Ghouta," said Maj. Gen. Vladimir Zolotukhin of the Russian center for reconciliation of Syria's warring parties.
They were the first recorded civilian evacuations from eastern Ghouta since government forces outlined a humanitarian corridor for escape more than one week ago. But there has been no let up to the shelling or bombardment to allow civilians to move.
Meanwhile, a “distress call” was issued on Saturday by Douma’s opposition-run local council.
"The bomb shelters and basements are full, and people are sleeping in the streets and in public gardens," said a statement addressed to international organisations.
"For three days, it has been hard to bury the dead because of the intense bombing on the cemetery.”
Eastern Ghouta – which is home to around 400,000 people – is the last remaining opposition-controlled zone on the outskirts of the capital, Damascus. Rebels have tried to counter the Assad forces’ offensive, but the government has steamrolled its efforts.
US Defense Secretary Jim Mattis on Sunday warned the Syrian government not to use chemical weapons in its civil war and said the Trump administration has made it clear that it would be "very unwise" to use gas in attacks.
Mr Mattis told reporters traveling with him to the Middle East that he was disturbed by reports of civilian casualties from bombings by regime militias.
"Right now we're getting reports — I don't have evidence that I can show you — but I'm aware of the reports of chlorine gas use," he said before arriving Sunday in Oman.
Syria’s conflict erupted with protests against Mr Assad but has since developed into a full-blown war drawing in world powers.
Russia has intervened on Mr Assad's behalf while Turkey has backed rebels against his regime.
Saturday, Ankara-backed rebels advanced against Kurdish militia in northwest Syria, coming to within two kilometres of the flashpoint town of Afrin, the Observatory said.
Elsewhere in Syria, the White Helmets rescue force suffered its first female fatality on Saturday, after air strikes hit a rebel-held town in Idlib province.