Duodenal atresia has a strong association with chromosomal anomalies, particularly trisomy 21. Duodenal atresia is identified prenatally in up to 60% of cases, and intestinal obstructions often present with signs, including difficulty feeding, emesis (particularly in the first 24 to 48 hours of life), abdominal distension, and inability to pass meconium in the immediate postnatal period. In this article, we present a simulated case of a neonate with trisomy 21 who presented at age 2 weeks for evaluation of poor weight gain and feeding intolerance and was diagnosed with duodenal atresia. Imaging is the mainstay of diagnosis and imaging modalities, such as abdominal radiographs or upper gastrointestinal studies, will reveal a “double bubble” sign. This sign indicates proximal dilation of the duodenum and stomach, suggesting duodenal atresia. Management often involves surgical correction to bypass the obstruction and parenteral nutrition, as enteral feeds are often introduced slowly postoperatively. Early diagnosis and a collaborative multidisciplinary approach are vital to successful treatment. [ Pediatr Ann . 2025;54(4):e139–e143.]
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