Etiology
Nausea and vomiting are common symptoms in children. The etiology of these symptoms is often age-dependent, with a wide spectrum of gastrointestinal, nongastrointestinal, and environmental causes.
Gastroenteritis
Gastroenteritis is a very common cause of nausea, vomiting, diarrhea, and abdominal pain.
Children ages <5 years may experience as many as 1-5 episodes of acute diarrhea each year.[5] According to the Global Health Data Exchange in 2016, gastroenteritis manifesting as diarrhea was the eighth leading cause of death worldwide among all ages (1.65 million deaths), and the fifth leading cause of death among children younger than 5 years (446,000 deaths).[6]
For pediatric patients in the US, around 1% of cases require hospitalization, often due to dehydration.[7] Thus, when feasible, the initial emphasis should be on the provision of oral rehydration for mild to moderate dehydration, and intravenous fluids for more severe cases.
Viral gastroenteritis: highly contagious infection that may present as an epidemic in a particular region and makes up 50% to 70% of cases of acute gastroenteritis. In most cases, the infection is self-limiting and resolves on its own, necessitating supportive measures only. The most common causative viral agents are norovirus, rotavirus, enteric adenovirus (types 40 and 41), astrovirus, coronavirus, and some picornaviruses.[8]
Bacterial gastroenteritis: infection generally produces more severe and prolonged symptoms. An estimated 15% to 20% of acute gastroenteritis episodes are thought to be caused by bacterial infection in the US, but stool studies are positive in only 1.5% to 5.6% of cases.[8][9] The most common causative bacteria are Salmonella, Shigella, Campylobacter, Escherichia coli, Vibrio, Yersinia, and Clostridium difficile.[8]
Parasitic gastroenteritis: parasitic infections are typically more prolonged and make up an estimated 10% to 15% of cases of acute gastroenteritis.[8] Giardiasis, an enteric infection caused by the protozoan parasite Giardia lamblia, is the most common parasitic infection and can be spread by ingestion of contaminated food or water, or person-to-person spread via the fecal-oral route. Other parasitic agents include Amoebas, Cryptosporidium, Isospora, Cyclospora, and Microsporidium.
Neurologic
Neurologic causes of nausea or vomiting are always concerning and often demand prompt evaluation and treatment.
Meningitis: a medical emergency. Frequently, the etiology is viral (e.g., enterovirus, arbovirus, herpes virus, influenza virus, and possibly mumps virus); bacterial meningitis (e.g., group B streptococcus, E coli, Listeria monocytogenes, Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis) is a rare, but more serious etiology.[10][11][12]
Functional neurologic syndromes: migraine, motion/travel sickness, and vertigo are very common. Pediatric migraines frequently lead to nausea and vomiting. The prevalence of migraine increases with age and has been estimated to be 8% to 23% between the ages of 10 and 20 years.[13]
Brain tumors: the second most common cause of malignancy in children, with a mortality rate varying from <10% to >90% depending on the lesion.[14] Etiology is variable; however, they can be associated with conditions such as neurofibromatosis or familial adenomatous polyposis.[15]
Intracranial hypertension: must be diagnosed and treated promptly; may be due to a brain tumor, pseudotumor cerebri (benign intracranial hypertension), hydrocephalus, infection, liver dysfunction, or ventriculoperitoneal shunt malfunction.[16]
Concussion (mild traumatic brain injury): relatively common during early childhood; nausea is frequently observed postconcussion.[17][18] Data from one large prospective observational cohort study indicate that approximately 13% of children (<18 years) experience vomiting following minor blunt head trauma.[19] Note that recurrent vomiting following mild head injury may predict intracranial injury.[20][21] In adolescents, concussion is frequently associated with blunt trauma due to athletic activities such as bicycling, football, basketball, and soccer.
Gastroenterologic: obstructive
Gastrointestinal obstruction is a common and very concerning cause of nausea and vomiting in children. The etiology is mostly age-dependent, but may also be contingent on pre-existing abdominal surgery.
Pyloric stenosis: incidence is around 2 per 1000 live births, with males having a 4- to 5-times increased risk compared with females.[22][23] Usually presents between 2 and 12 weeks of age.[22][24][25] A family history of a parent having the condition is common.[26][27]
Small bowel atresia: commonly associated with polyhydramnios and diagnosed prenatally. Presentation occurs soon after birth with abdominal distention and vomiting.
Intestinal malrotation: a spectrum of rotational and fixation disturbances that can occur during embryonic development. Has an incidence of 1 per 6000 live births and is considered as a surgical emergency. Can lead to a midgut volvulus with a high risk of intestinal necrosis.
Intussusception: the most common cause of intestinal obstruction in children ages 6-36 months old, with an incidence of 36 cases per 100,000 infant years in the US.[28] It is always considered an emergency. While usually idiopathic in etiology, viral diseases have been associated with triggering an acute episode.[29]
Superior mesenteric artery syndrome: an uncommon cause of small bowel obstruction. In this condition, a functional compression exists of the third portion of the duodenum by the superior mesenteric artery and the aorta. It is commonly associated with a slim body habitus, a recent and marked history of weight loss, or a history of spinal surgery.[30]
Gastroenterologic: functional
Gastroesophageal reflux disease: simple regurgitation occurs in almost 50% of infants. In 90% of these infants, symptoms are limited to oral regurgitations and resolve by the age of 1 year in most.[31]
Cyclic vomiting: defined as a pattern of intermittent and often paroxysmal vomiting, alternating with asymptomatic periods without vomiting.[32] It is a diagnosis of exclusion and can only be diagnosed in patients after the exclusion of inflammatory, metabolic, or neoplastic causes. It is frequently seen in children, particularly adolescents and females, with an estimated prevalence of approximately 2% in school-aged children.[32][33] Initially, episodes may be confused for a prolonged viral gastroenteritis. Suspicion should arise when the stereotypical pattern is established.[34]
Dysautonomia (e.g., postural orthostatic tachycardia syndrome and orthostatic hypotension): while primary dysautonomic syndromes are extremely rare, the presence of nausea and vomiting in these syndromes is common in adolescents; up to 87% of pediatric patients with orthostatic intolerance report gastrointestinal symptoms.[35]
Gastroparesis: defined as delayed gastric emptying and associated with nausea and vomiting. It is an uncommon cause of vomiting in children. It frequently occurs after a viral infection (i.e., postviral gastroparesis), but may be seen in association with mitochondrial, neuromuscular, and autoimmune disorders.
Hirschsprung disease: a congenital condition, affecting the distal segments of the colon, caused by absence of ganglion cells in the myenteric and submucosal plexus. This creates a functional obstruction. It occurs in 1 in 5000 live births and is generally associated with frequent episodes of enterocolitis.[36]
Constipation: prevalence of 0.7% to 29.6% worldwide in children.[37][38] Rarely, it can lead to symptoms suggesting bowel obstruction, particularly in the presence of marked impaction of stool in the rectum. However, it is better recognized as a "functional" versus "true" mechanical obstruction, despite the relative similarity in presentation.
Functional dyspepsia: presence of epigastric pain or discomfort associated with early satiety, nausea, or vomiting. It occurs in the absence of inflammatory or metabolic disease or malignancy that would otherwise explain the symptoms. Symptoms may in part be explained by abnormalities in antroduodenal motility, gastric emptying, gastric sensation, and accommodation.
Gastroenterologic: inflammatory
Peptic ulcer disease: common in certain pediatric populations. Helicobacter pylori is a frequent cause and is often associated with a family history of infection, low socioeconomic status, or crowded living conditions.[39] It is also common in the setting of an acute illness (e.g., patients in intensive care units).
Acute appendicitis: usually caused by an obstruction (e.g., lymphoid hyperplasia, fecalith) of the lumen of the appendix.
Acute pancreatitis: the most common causes in children include mutations in genes encoding proteases, congenital anomalies affecting the pancreas, gallstones, and drugs (e.g., valproic acid, glucocorticoids).[40]
Hepatitis A: infection caused by the hepatitis A virus, an RNA virus, spread via close contact with an infected person (including fecal-oral contact) or contaminated food or water.
Gastroenterologic: allergic
Food allergies: the incidence of food allergies is approximately 10% at 1 year of age, falling to 3% to 4% by the age of 2 years.[41] Some children demonstrate persistent symptoms with associated respiratory and dermatologic complaints. Milk/dairy (lactose), wheat, soy, peanuts, eggs, and shellfish are the most frequently involved foods.
Eosinophilic esophagitis: defined as the presence of ≥15 eosinophils per high-power field in an esophageal biopsy with presence of esophageal dysfunction, in the absence of other causes of esophageal eosinophilia.[42][43][44] Prevalence has increased over time.[45] Food allergies seem to play a major role in the pathogenesis of the disease; however, the etiology is not clearly defined.
Gastroenterologic: malignancy
Small bowel lymphoma: predisposing factors such as low socioeconomic status, poor sanitation, and genetic factors have been associated with the development of immune-proliferative small intestine disease. Celiac disease and ulcerative enteritis are more closely linked to enteropathy-associated T-cell lymphoma.[46]
Metabolic/endocrine
Diabetic ketoacidosis: more common in children <5 years of age and girls, and is more frequently the initial presentation for type 1 (versus type 2) diabetes.[47][48]
Adrenal insufficiency: rare in children. Nausea and vomiting are common presenting symptoms.[49] Adrenal insufficiency has been linked to syndromes such as congenital adrenal hyperplasia, triple A syndrome (achalasia, addisonianism, and alacrima), autoimmune adrenal failure, and paroxysmal disorders.
Inborn errors of metabolism: uncommon disorders that generally present at birth and may be devastating if unrecognized. Protein metabolism disorders include aminoaciduria, organic acidemias, and urea cycle disorders, and are associated with poor feeding, vomiting, and lethargy. They can also be associated with metabolic decompensation including acidosis, hyperammonemia, or hypoglycemia. If not treated, disease progression including neurologic compromise and death may occur. Carbohydrate metabolism disorders include galactosemia, fructosemia, and some glycogen storage diseases, and can result in poor feeding, vomiting, liver dysfunction, and hypoglycemia.[50]
Urologic/gynecologic and renal
Nausea and vomiting are frequent symptoms of renal, urologic, and gynecologic diseases.
Gonadal torsion: testicular or ovarian torsion are considered surgical emergencies. Testicular torsion is more common between the ages of 12 and 18 years; however, it can occur in young infants and neonates as well.[51] It can be due to trauma. Ovarian torsion generally occurs just before menarche, but may also occur in younger girls. Approximately 25% of patients have normal ovaries; however, more commonly, the condition is associated with ovarian cysts or benign masses.[52]
Urinary tract infection (UTI): estimated prevalence in children is approximately 7%.[53] Occurs most frequently in females. Bacterial infection is the most common cause. Risk factors include chronic constipation, bladder dysfunction (e.g., neurogenic bladder), and vesicoureteral reflux.
Hemolytic uremic syndrome: a common cause of kidney failure in children, which is commonly associated with O157 H7 toxigenic E coli and Shigella infection. Genetic and medication-related causes also exist.[54] Mortality can reach 5%, and chronic renal failure can occur in 20% of patients.[55]
Nephrolithiasis: incidence is increasing in children. More frequently seen in white boys, with most patients aged 13 years or younger.[56] Risk factors include: environmental factors; metabolic conditions; systemic disorders; structural abnormalities of the kidneys, ureters, or bladder; and a history of UTIs. The most frequent composition is calcium oxalate and phosphate.[57]
Ureteropelvic junction obstruction: an obstruction of the flow of urine from the renal pelvis to the proximal ureter, which is frequently diagnosed prenatally. Causes include congenital abnormalities, previous surgery, or disorders that cause inflammation of the upper urinary tract.
Psychiatric
Eating disorders: the lifetime prevalence of bulimia nervosa (DSM criteria) has been estimated to be up to 4.6% for females and 1.3% for males, and up to 3.6% and 0.3%, respectively, for anorexia nervosa (DSM criteria).[58][59] Eating disorders have an associated mortality of 2% to 6%, with adolescents being at increased risk.[60][61] It is commonly associated with depression and other psychiatric comorbidities.
Rumination syndrome: defined as the presence of repeated oral regurgitation of small amounts of food from the stomach, which is often then re-swallowed. This usually occurs during or immediately after the patient eats. It is found in approximately 5% of the pediatric population and is frequently associated with psychiatric disorders such as bulimia nervosa.[62][63][64] It occurs more commonly in children with developmental delays.[65]
Factitious disorder (medical abuse): should be suspected when symptoms seem fabricated or out of proportion to the examination. Often, routine diagnostic workup does not explain the nature of the symptoms. Nausea and vomiting are common in this disorder. It occurs frequently in children ages <5 years. The perpetrator is often one of the child’s parents or caretakers. It can be devastating if not recognized early.[66]
Environmental
Toxic ingestions: approximately 1.17 million toxic exposures in children (<20 years) were reported by poison control centers in the US in 2021.[67] Among the most common exposures in children age ≤5 years were cosmetics, cleaning substances, analgesics, pesticides, cough and cold preparations, cardiovascular drugs, stimulants and street drugs, and essential oils.[67]
Medication adverse effects: the most common include chemotherapy drugs (induce stimulation of the area postrema in the hypothalamus and may produce severe symptoms), opioid analgesics (due to their effect on reducing gastrointestinal motility), and anticholinergic medications such as antidepressants or antispasmodics (due to reducing gastrointestinal motility). Nonsteroidal anti-inflammatory drugs can cause nausea and vomiting secondary to gastrointestinal inflammation. Others include anesthetics and antibiotics.
Respiratory/ear, nose, and throat
Otitis media: defined as the presence of fluid and inflammation in the middle ear. Very common in the pediatric population, with 1 in 4 children having at least 1 episode of acute otitis media by the age of 10 years.[71] The most common pathogens associated with acute otitis media are bacteria such as S pneumoniae, H influenza, and Moraxella catarrhalis; however, viruses have also been implicated.
Pneumonia: a very common cause of morbidity in children. It is more frequent in boys aged <5 years, particularly in association with a low socioeconomic status. Both viruses (e.g., influenza virus) and bacteria (e.g., S pneumonia, Mycoplasma pneumoniae) have been implicated.
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