The number of children who were injured increased by 25 percent since 2015. The report comes as the conflict in Syria enters its sixth year.
UNICEF verified 850 cases of children being recruited to fight in the conflict, about double the 2015 figure.
According to the United Nations Children's Fund (UNICEF), at least 652 children were killed previous year - a 20 per cent increase compared to 2015 - 255 among them were killed in or near a school.
It has labelled the depth of suffering "unprecedented", adding that "Each and every child is scarred for life with horrific consequences on their health, well-being and future".
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"Targeting of health facilities and health staff increased sharply in 2016, killing and injuring hundreds of medical personnel and civilians", Bachir Tajaldin, an internist in Syria, said in the UNICEF report.
UNICEF said kids were being forced into combat roles, including acting as prison guards and even executioners or suicide bombers.
UNICEF said that the data included in the report comprised exclusively of verified cases, and that the actual scale of the suffering documented was likely to be higher.
"Luckily, and thanks to the determination of the people of Syria - parents, fathers, mothers, teachers - thanks to the support of host governments, children are able to go back to school, they are able to resume their studies, catch up on what they've lost".
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Education and medical treatment are becoming even more hard to access, and as a result, more families are turning to drastic measures for survival.
"Millions of children in Syria come under attack on a daily basis, their lives turned upside down".
"Children have paid the heaviest price in this six-year war and their suffering hit rock bottom last year in a drastic escalation of violence", UNICEF wrote. In 2016, 12,600 school children crossed risky conflict lines, many traveling for days, so that they could take their final exams.
On 13th March, UNICEF released a new assessment of what it calls "grave violations against children in Syria".
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"Over the a year ago in Syria, all parties involved have blocked vital aid supplies and millions have become poorer, hungrier and more isolated from assistance and from the world", said NRC's Mideast director, Carsten Hansen, according to The Associated Press.