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Objective To investigate the prenatal diagnosis, perinatal management and standardized treatment protocol for neonates with duodenal obstruction. Methods A network in prenatal diagnosis, perinatal management and monitoring of congenital malformation was founded between Beijing Obstetrics and Gynecology Hospital and the Capital Institute of Pediatrics. Forty-four fetuses were prenatally diagnosed as duodenal obstructions by this network from July,2001 to September, 2010. The data of prenatal diagnosis, treatment after birth and prognosis were analyzed. Results Among 44 patients diagnosed as fetal duodenal obstruction by prenatal ultrasonography, three cases underwent induced abortion, three were in pregnancy, 14 were lost during follow-up and 24 were confirmed by surgical treatments after birth. Within 24 neonates underwent surgery, 21 showed double-bubble sign and 20 combined with polyhydroamnios in prenatal ultrasonography. Twenty-four neonates underwent upright abdominal plain film examination,22 showed double-bubble sign, 1 showed single-bubble sign and 1 showed triple-bubble sign,respectively. Nineteen neonates underwent upper gastroenterography which showed distention of stomach and duodenum, increased stomach peristalsis and an obstacle of duodenum emptying. Within 23 neonates underwent ultrasonographic studies, 10 showed distention and increased peristalsis of duodenum. Following surgical procedures were performed: diamond shape anastomosis was completed in 19 cases with annular pancreas; duodenal vertical resection, across suture and excision of the membrane was done in four cases with duodenum membranate stenosis; end-to-back anastomosis was taken in one case with duodenal separate atresia; Ladd's procedure was applied in 11 cases associated with malrotation. All patients were cured. Conclusions Standardized perinatal management and earlier intervention should be offered to newborns with duodenal obstruction to achieve better effects.