Relevant articles in the international literature, retrieved from PubMed from 1977 to the present, were identified using the keywords gastrointestinal hemorrhage, upper GI bleeding, massive hemorrhage, massive transfusion, newborn, hematemesis, endoscopy, hematochezia, and peptic ulcer. We reviewed 23 articles and identified 29 cases of neonatal massive UGI bleeding [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]. We integrated the cases reported in these articles by evaluating their clinical manifestations, comorbidities, diagnoses, and treatments (Table 1).

Table 1 Demographics, clinical features, risk factors, and outcome in neonates with massive UGI bleeding (n = 29)

Gastrointestinal bleeding in neonates and infants under 1 year of age has unique etiologies. The common cause of gastrointestinal bleeding in healthy neonates is swallowing maternal blood (from cracked nipples) [1, 9, 17, 24,25,26]. Therefore, to differentiate the source of bleeding, the Apt-Downey test can be applied. The mother of our patient did not have any nipple fissures, which ruled out the possibility of the bleeding originating from the mother.

Coagulopathy, thrombocytopenia, and stress gastritis or ulcers are common causes of gastrointestinal hemorrhage [5, 27, 28]. Among the cases we have documented, diffuse hemorrhagic gastritis and peptic ulcers were found in 18 cases (62.07%). Neonatal peptic ulcers are categorized into primary and secondary types, with secondary ulcers being more common and often caused by stress or medications, such as physiological stresses like shock, respiratory failure, hypoglycemia, cow milk protein intolerance, major surgery, and sepsis. Perinatal stress (such as asphyxia, prenatal medication use, prolonged labor, use of obstetric instruments, or psychosocial stress) can also lead to ulcers [1,2,3, 9, 11, 19, 28,29,30]. These stressors can disrupt gastric mucosal homeostasis, resulting in ulcer formation. Among the 29 reported cases, 4 were associated with these stressors. Gastrointestinal bleeding in neonates due to vitamin K deficiency may be related to the mother’s use of antibiotics or vitamin K antagonists during pregnancy [2, 6, 25]. In our case, the mother had no history of medication use during pregnancy, and the neonate was administered vitamin K after birth and following upper gastrointestinal bleeding, which helps reduce the risk of bleeding caused by vitamin K deficiency.

If a healthy neonate suddenly experiences acute gastrointestinal bleeding, Dieulafoy lesions (DL), gastrointestinal vascular malformations, or Meckel’s diverticulum may also need to be considered [8, 13, 18, 23, 26, 28]. Among the 29 reported cases, 4 were attributed to uncommon etiologies of hemorrhage.

Massive upper gastrointestinal bleeding typically manifests as hematemesis, melena, or hematochezia. Hematemesis can be either bright red blood or a coffee-ground-like substance. When hemoglobin is digested by digestive enzymes, it results in melena. However, if UGI bleeding is too rapid, hematochezia may appear. It has been reported that among every 10 patients with hematochezia, one may have upper gastrointestinal bleeding [12, 17, 25,26,27,28,29,30,31]. Among these 29 cases, 24 (82.76%) patients presented with hematemesis, 3 (10.34%) with melena, and 2 (6.90%) with fresh blood on the nasogastric tube. Our patient presented with both hematemesis and melena.

Acute gastric peptic ulcers can be managed conservatively [25]. A gastric pH below 2.5 is one of the risk factors for stress ulcers and gastrointestinal bleeding [1, 27]. Proton pump inhibitors (PPIs) and histamine-2 (H₂) receptor antagonists can significantly increase gastric pH and improve UGI bleeding in neonates [2, 6, 26, 29]. Additionally, PPI can reduce the rebleeding rate, blood transfusion requirements, and hospital stay for children with UGI bleeding caused by gastric or duodenal ulcers [1, 2, 5, 24, 25, 27–39, 31]. Among these 29 cases, 9 (31.03%) patients were treated with H₂ receptor antagonists (including our case) and 5 (17.24%) with PPI; Octreotide is a somatostatin analog that has been proven to alleviate gastrointestinal bleeding in children and is safe and effective for severe non-arterial gastrointestinal bleeding [25, 28, 29, 31]. Among these 29 cases, 1 (3.45%) patient received octreotide.

Massive UGI bleeding typically leads to poor blood perfusion of terminal organs, resulting in organ damage [28]. Infusion of red blood cells can maintain hemoglobin levels to transport oxygen to tissues. Neonates have a lower blood volume compared to adults, and massive UGI bleeding can rapidly worsen their condition. More importantly, the measured hemoglobin concentration lags behind the actual hemoglobin level, making it unreliable in the presence of active bleeding [25, 28]. Therefore, some studies suggest that early blood transfusion should be considered in cases of massive UGI bleeding [25, 26, 28, 29]. Among these 29 cases, 12 (41.38%) had low hematocrit, 16 (55.17%) had hemoglobin < 150 g/L, and 26 (89.66%) received transfusions. Among them, 4 (13.79%) received a transfusion volume exceeding their calculated blood volume, and 8 (27.59%) were transfused with fresh frozen plasma. Our patient received a transfusion of 260 ml of packed red blood cells, which exceeded his calculated blood volume (240 ml).

If conservative treatment fails, exploration is necessary. Nowadays, gastrointestinal endoscopy has become a preferred method for investigating major gastrointestinal bleeding, as it can identify the specific cause of gastrointestinal bleeding in children, even in neonates [2, 4, 6, 23, 25,26,27,28,29,30,31,32]. It can also provide targeted treatment for specific etiologies, such as varices and ulcers [20, 25, 27, 28]. Among the 29 reported cases, 6 underwent endoscopic procedures. However, upper gastrointestinal endoscopy may not be suitable for neonates with massive UGI bleeding due to their severe conditions and technical difficulty.

If the above measures fail to control the massive UGI bleeding, surgical treatment should be required [8, 14, 26, 29]. Currently, there are several surgical options, including suture ligation of the bleeding points in the mucosa, vagotomy alone, vagotomy with pyloroplasty, radical subtotal gastrectomy, total gastrectomy, and gastric devascularization [2, 9, 14, 16]. Radical subtotal gastrectomy and total gastrectomy are not suitable for neonates and growing children. Vagotomy alone and vagotomy with pyloroplasty are feasible and do not have long-term adverse effects on the children’s growth and development. Diffuse massive bleeding may necessitate a total gastrectomy. The rebleeding rate after vagotomy is high, and the mortality rate associated with subtotal gastrectomy is also high. In children, especially in small babies, these procedures might have adverse effects on their nutrition, growth, and development [14, 16, 33, 34]. Studies have found that acute erosive-hemorrhagic gastritis is associated with gastric mucosa congestion rather than local ischemia. Experiments have confirmed that the total blood flow of the gastric mucosa immediately decreases after gastric devascularization [35]. This procedure has been applied in neonates, with satisfactory hemostasis effect and long-term outcome [14, 35]. Among the 29 reported cases, 9 underwent surgery. In our patient, intraoperative findings showed massive upper gastrointestinal bleeding caused by acute diffuse hemorrhagic gastritis. We chose gastric devascularization as an option with good results in a one-year follow-up period after surgery. In the reviewed literature, the cases using gastric devascularization [14, 35] are similar to our cases: bleeding could not be controlled after conservative treatment; operative findings confirmed the cause of bleeding was acute diffuse hemorrhagic gastritis; both cases achieved hemostasis, with no recurrent bleeding, with a good outcome. Gastric devascularization is not technically difficult, and when surgical exploration confirms acute diffuse hemorrhagic gastritis as the source of bleeding, gastric devascularization may be considered as an alternative to simple vagotomy or vagotomy with pyloroplasty for neonatal hemorrhagic gastritis [14]. Although gastric devascularization has yielded good results, it still has some potential risks, such as the possibility of gastric ischemia, necrosis, or rebleeding after surgery [9, 14, 33,34,35].

In conclusion, massive UGI bleeding in neonates is a rare but life-threatening condition. Hematemesis and/or melena accompanied by hemodynamic instability should raise a suspicion of UGI bleeding. Stress gastritis and ulcers are common causes. If the patient’s status is stable after blood transfusion, early endoscopic assessment might be an option for accurate diagnosis and precise management. In cases with uncontrolled bleeding, surgery remains a vital option for the management of massive UGI bleeding in neonates. However, prospective randomized clinical studies are needed.