| Item of concern | Why it is concerning |
|---|---|
| Consanguinity | Increased risk of autosomal recessive disorders. |
| Neonatal cholestasis in the parents or siblings | Cystic fibrosis, alpha-1 antitrypsin deficiency, progressive familial intrahepatic cholestasis, and Alagille syndrome are all genetic conditions causing neonatal cholestasis. |
| Family history of repeated fetal loss or early demise | Suggestive of gestational alloimmune liver disease. |
| Spherocytosis and other hemolytic diseases | Known to aggravate conjugated hyperbilirubinemia. |
| Prenatal ultrasonography findings | Presence of choledochal cyst, cholelithiasis, bowel anomalies, or concern for a syndrome. |
| Maternal cholestasis of pregnancy | May be seen in heterozygotes for PFIC gene mutations; may also suggest mitochondrial disorders. |
| Maternal acute fatty liver of pregnancy | Associated with neonatal long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency. |
| Maternal infections | TORCH infections (Toxoplasmosis, “other”/syphilis, Rubella, CMV, HSV). |
| Gestational age | Prematurity is a risk factor for neonatal hepatitis. |
| Small for gestational age (SGA) | Increased risk of neonatal cholestasis and congenital infections. |
| Alloimmune hemolysis; G6PD deficiency; hydrops fetalis | Increased risk of neonatal cholestasis. |
| Neonatal infection | Urinary tract infection, sepsis-related cholestasis, CMV, HIV, syphilis, etc. |
| Newborn screen abnormalities | Panhypopituitarism, galactosemia, fatty acid oxidation defects, cystic fibrosis. |
| Source of nutrition: breast milk, formula, parenteral nutrition (PN) | Galactosemia, hereditary fructose intolerance, and PN-associated liver disease. |
| Appearance | Dysmorphic features suggestive of syndromes such as Alagille’s (consider murmur). |
| Growth | May indicate underlying genetic or metabolic disease. |
| Vision | Septo-optic dysplasia and optic nerve hypoplasia, often associated with panhypopituitarism. |
| Hearing | Associated with PFIC1, TJP2 and other cholestatic disorders. |
| Vomiting | May indicate metabolic disease, bowel obstruction, or pyloric stenosis. |
| Stooling pattern | Delayed stooling: cystic fibrosis, panhypopituitarism (check genitalia); diarrhea: infection or metabolic disease. |
| Stool color | Acholic stools suggest biliary obstruction and cholestasis. |
| Urine characteristics: smell and color | Dark urine suggests conjugated hyperbilirubinemia or metabolic disease. |
| Excessive bleeding | May indicate coagulopathy or vitamin K deficiency. |
| Disposition: irritability, lethargy | May reflect metabolic disease, sepsis, or panhypopituitarism. |
| History of abdominal surgery | Necrotizing enterocolitis, intestinal atresia, or other surgical conditions affecting the biliary tree or intestine. |
| Neonatal exposure to fluconazole or micafungin | Drugs that can cause cholestasis. |