"Breastfeeding jaundice" or "lack of breastfeeding jaundice," is caused by insufficient breast milk intake, resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This leads to increased enterohepatic circulation, resulting in increased reabsorption of bilirubin from the intestines. Usually occurring in the first week of life, most cases can be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production.

Prolonged hyperbilirubinemia (severe jaundice) can result in chronic bilirubin encephalopathy (kernicterus). Quick and accurate treatment of neonatal jaundice helps to reduce the risk of neonates developing kernicterus.

Infants with kernicterus may have a fever or seizures. High pitched crying is an effect of kernicterus. Scientists used a computer to record and measure cranial nerves 8, 9 and 12 in 50 infants who were divided into two groups equally depending upon bilirubin concentrations. Of the 50 infants, 43 had tracings of high pitched crying.

Exchange transfusions performed to lower high bilirubin levels are an aggressive treatment.

Yellow discoloration of the skin, especially on the palms and the soles, but not of the sclera or inside the mouth is due to carotenemia—a harmless condition.

"Pre-hepaticular" jaundice is caused by anything which causes an increased rate of hemolysis (breakdown of red blood cells). Unconjugated bilirubin comes from the breakdown of the heme pigment found in red blood cells' hemoglobin. The increased breakdown of red blood cells leads to an increase in the amount of unconjugated bilirubin present in the blood and deposition of this unconjugated bilirubin into various tissues can lead to a jaundiced appearance. In tropical countries, severe malaria can cause jaundice in this manner. Certain genetic diseases, such as sickle cell anemia, spherocytosis, thalassemia, pyruvate kinase deficiency, and glucose 6-phosphate dehydrogenase deficiency can lead to increased red cell lysis and therefore hemolytic jaundice. Commonly, diseases of the kidney, such as hemolytic uremic syndrome, can also lead to coloration.

In jaundice secondary to hemolysis, the increased production of bilirubin leads to the increased production of urine-urobilinogen. Bilirubin is not usually found in the urine because unconjugated bilirubin is not water-soluble, so, the combination of increased urine-urobilinogen with no bilirubin (since, unconjugated) in urine is suggestive of hemolytic jaundice.

Laboratory findings include:

- Urine: no bilirubin present, urobilinogen > 2 units (i.e., hemolytic anemia causes increased heme metabolism; exception: infants where gut flora has not developed).

- Serum: increased unconjugated bilirubin.

- Kernicterus is associated with increased unconjugated bilirubin not carried by albumin. Newborns are especially vulnerable to this due to increased permeability of the blood brain barrier.

Infants with neonatal hepatitis caused by the cytomegalovirus, rubella or the hepatitis A, B, and C viruses may transmit the infection to others who come in close contact with the infant.

These infected infants should not come into contact with pregnant women because of the possibility that the woman will transmit the virus to her unborn child.

In the 80 percent of the cases where there is no virus identified as the cause.

Estrogens, and particularly glucuronides such as estradiol-17β-D-glucuronide, have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes.

The causes of intrahepatic cholestasis of pregnancy are still not fully understood. Hormones and genetic factors are likely to be important in the pathogenesis of the disease. A number of features of the disease suggest a link to hormones:

- ICP occurs in the third trimester at the time when hormone levels are at their highest.

- Twin and triplet pregnancies, which are associated with higher hormone levels, show a higher incidence of ICP.

- ICP resolves quickly after delivery, when placental hormone production ceases.

- Older high-dose estrogen oral contraceptive pills could cause features of ICP.

Gilbert's syndrome and G6PD deficiency occurring together especially increases the risk for kernicterus.

Liver disease can occur through several mechanisms. A common form of liver disease is viral infection. Viral hepatitides such as Hepatitis B virus and Hepatitis C virus can be vertically transmitted during birth via contact with infected blood. According to a 2012 NICE publication, "about 85% of hepatitis B infections in newborns become chronic". In occult cases, Hepatitis B virus is present by HBV DNA, but testing for HBsAg is negative. High consumption of alcohol can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty liver disease, cirrhosis, and liver cancer. In the earlier stages of alcoholic liver disease, fat builds up in the liver's cells due to increased creation of triglycerides and fatty acids and a decreased ability to break down fatty acids. Progression of the disease can lead to liver inflammation from the excess fat in the liver. Scarring in the liver often occurs as the body attempts to heal and extensive scarring can lead to the development of cirrhosis in more advanced stages of the disease. Approximately 3–10% of individuals with cirrhosis develop a form of liver cancer known as hepatocellular carcinoma.

According to Tilg, et al., gut microbiome could very well have an effect, be involved in the pathophysiology, on the various types of liver disease which an individual may encounter.

There are more than a hundred different kinds of liver disease. Symptoms may include jaundice and weight loss. These are some of the most common:

- Fascioliasis, a parasitic infection of liver caused by a Liver fluke of the "Fasciola" genus, mostly the "Fasciola hepatica".

- Hepatitis, inflammation of the liver, is caused by various viruses (viral hepatitis) also by some liver toxins (e.g. alcoholic hepatitis), autoimmunity (autoimmune hepatitis) or hereditary conditions.

- Alcoholic liver disease is a hepatic manifestation of alcohol overconsumption, including fatty liver disease, alcoholic hepatitis, and cirrhosis. Analogous terms such as "drug-induced" or "toxic" liver disease are also used to refer to disorders caused by various drugs.

- Fatty liver disease (hepatic steatosis) is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells. Non-alcoholic fatty liver disease is a spectrum of disease associated with obesity and metabolic syndrome.

- Hereditary diseases that cause damage to the liver include hemochromatosis, involving accumulation of iron in the body, and Wilson's disease. Liver damage is also a clinical feature of alpha 1-antitrypsin deficiency and glycogen storage disease type II.

- In transthyretin-related hereditary amyloidosis, the liver produces a mutated transthyretin protein which has severe neurodegenerative and/or cardiopathic effects. Liver transplantation can give a curative treatment option.

- Gilbert's syndrome, a genetic disorder of bilirubin metabolism found in a small percent of the population, can cause mild jaundice.

- Cirrhosis is the formation of fibrous tissue (fibrosis) in the place of liver cells that have died due to a variety of causes, including viral hepatitis, alcohol overconsumption, and other forms of liver toxicity. Cirrhosis causes chronic liver failure.

- Primary liver cancer most commonly manifests as hepatocellular carcinoma and/or cholangiocarcinoma; rarer forms include angiosarcoma and hemangiosarcoma of the liver. (Many liver malignancies are secondary lesions that have metastasized from primary cancers in the gastrointestinal tract and other organs, such as the kidneys, lungs.)

- Primary biliary cirrhosis is a serious autoimmune disease of the bile capillaries.

- Primary sclerosing cholangitis is a serious chronic inflammatory disease of the bile duct, which is believed to be autoimmune in origin.

- Budd–Chiari syndrome is the clinical picture caused by occlusion of the hepatic vein.

Unconjugated hyperbilirubinemia during the neonatal period describes the history of nearly all individuals who suffer from kernicterus. It is thought that the blood–brain barrier is not fully functional in neonates and therefore bilirubin is able to cross the barrier. Moreover, neonates have much higher levels of bilirubin in their blood due to:

1. Although the severe anemia of erythroblastosis fetalis is usually the cause of death, many children who barely survive the anemia exhibit permanent mental impairment or damage to motor areas of the brain because of precipitation of bilirubin in the neuronal cells, causing destruction of many, a condition called kernicterus. The rapid breakdown of fetal red blood cells immediately prior to birth (and subsequent replacement by normal adult human red blood cells). This breakdown of fetal red blood cells releases large amounts of bilirubin. Following on from this

2. Neonates cannot metabolize and eliminate bilirubin. The sole path for bilirubin elimination is through the uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1) proteins that perform a (SN2 conjugation) reaction called "glucuronidation". This reaction adds a large sugar to the bilirubin and makes it more water-soluble, so more readily excreted via the urine and/or the feces. The UGT1A1 enzymes are present, but not active until several months after birth in the newborn liver. Apparently, this is a developmental compromise since the maternal liver and placenta perform glucuronidation for the fetus. In the early 1980s a late-fetal change (30 – 40 weeks of gestation) in hepatic UGT1A1 (from 0.1% to 1.0% of adult activity levels) and post-natal changes that are related to birth age not gestational age were reported. Similar development of activities to pan-specific substrates were observed except for serotonin (1A4), where adult activities were observed in fetal (16 – 25 weeks) and neonatal liver up to 10 days old. More recently, individual UGT isoform development in infants and young children, including two fetal liver samples, were analyzed and showed that pediatric levels of mRNA and protein for UGT1A1 did not differ from adults, but activities were lower. Hence, the effects of UGT1A1 developmental delay in activation have been illuminated over the last 20–30 years. The molecular mechanism(s) for activating UGT1A1 remain unknown.

3. Administration of aspirin to neonates and infants. Aspirin displaces the bilirubin that was non-covalently attached to albumin in the blood stream, thus generating an increased level of free bilirubin which can cross the developing blood brain barrier. This can be life-threatening.

Bilirubin is known to accumulate in the gray matter of neurological tissue where it exerts direct neurotoxic effects. It appears that its neurotoxicity is due to mass-destruction of neurons by apoptosis and necrosis.

A study performed at Strong Memorial Hospital in Rochester, New York, showed that infants ≤ 60 days old meeting the following criteria were at low-risk for having a serious bacterial illness:

- generally well-appearing

- previously healthy

- full term (at ≥37 weeks gestation)

- no antibiotics perinatally

- no unexplained hyperbilirubinemia that required treatment

- no antibiotics since discharge

- no hospitalizations

- no chronic illness

- discharged at the same time or before the mother

- no evidence of skin, soft tissue, bone, joint, or ear infection

- White blood cells (WBCs) count 5,000-15,000/mm

- absolute band count ≤ 1,500/mm

- urine WBC count ≤ 10 per high power field (hpf)

- stool WBC count ≤ 5 per high power field (hpf) "only in infants with diarrhea"

Those meeting these criteria likely do not require a lumbar puncture, and are felt to be safe for discharge home without antibiotic treatment, or with a single dose of intramuscular antibiotics, but will still require close outpatient follow-up.

One risk for Group B streptococcal infection (GBS) is Preterm rupture of membranes. Screening women for GBS (via vaginal and rectal swabbing) and treating culture positive women with intrapartum chemoprophylaxis is reducing the number of neonatal sepsis caused by GBS.

Gilbert's syndrome (GS) is a mild liver disorder in which the liver does not properly process bilirubin. Many people never have symptoms. Occasionally a slight yellowish color of the skin or whites of the eyes may occur. Other possible symptoms include feeling tired, weakness, and abdominal pain.

Gilbert's syndrome is due to a mutation in the UGT1A1 gene which results in decreased activity of the bilirubin uridine diphosphate glucuronosyltransferase enzyme. It is typically inherited in an autosomal recessive pattern and occasionally in an autosomal dominant pattern depending on the type of mutation. Episodes of jaundice may be triggered by stress such as exercise, menstruation, or not eating. Diagnosis is based on higher levels of unconjugated bilirubin in the blood without either signs of other liver problems or red blood cell breakdown.

Typically no treatment is needed. If jaundice is significant phenobarbital may be used. Gilbert's syndrome affects about 5% of people in the United States. Males are more often diagnosed than females. It is often not noticed until late childhood to early adulthood. The condition was first described in 1901 by Augustin Nicolas Gilbert.

The mechanism of hepatomegaly consists of vascular swelling, inflammation (due to the various causes that are infectious in origin) and deposition of (1) non-hepatic cells or (2) increased cell contents (such due to iron in hemochromatosis or hemosiderosis and fat in fatty liver disease)

The enzymes that are defective in GS - UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) - are also responsible for some of the liver's ability to detoxify certain drugs. For example, Gilbert's syndrome is associated with severe diarrhea and neutropenia in patients who are treated with irinotecan, which is metabolized by UGT1A1.

While paracetamol (acetaminophen) is not metabolized by UGT1A1, it is metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity.

Biliary atresia, also known as extrahepatic ductopenia and progressive obliterative cholangiopathy, is a childhood disease of the liver in which one or more bile ducts are abnormally narrow, blocked, or absent. It can be congenital or acquired. As a birth defect in newborn infants, it has an incidence of one in 10,000–15,000 live births in the United States, and a prevalence of one in 16,700 in the British Isles. Biliary atresia is most common in East Asia, with a frequency of one in 5,000.

The causes of biliary atresia are not well understood. Congenital biliary atresia has been associated with certain genes, while acquired biliary atresia is thought to be a result of an autoimmune inflammatory response, possibly due to a viral infection of the liver soon after birth. The only effective treatments are surgeries such as the Kasai procedure and liver transplantation.

Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass. Depending on the cause, it may sometimes present along with jaundice.

An association between biliary atresia and the ADD3 gene was first detected in Chinese populations through a Genome-wide association study, and was confirmed in Thai Asians and Caucasians. A possible association with deletion of the gene GPC1, which encodes a glypican 1-a heparan sulfate proteoglycan, has been reported. This gene is located on the long arm of chromosome 2 (2q37) and is involved in the regulation of inflammation and the Hedgehog gene.

Neonates with biliary atresia were found to have null GSTM1 genotype while all their moms were heterozygous for GSTM1. Thus these infants are protected intrauterine by their maternal detoxification system, yet once born they cannot handle the detoxification of aflatoxin load.

α-antitrypsin deficiency has been associated with a number of diseases:

- Cirrhosis

- COPD

- Pneumothorax

- Asthma

- Granulomatosis with polyangiitis

- Pancreatitis

- Gallstones

- Bronchiectasis

- Pelvic organ prolapse

- Primary sclerosing cholangitis

- Autoimmune hepatitis

- Emphysema, predominantly involving the lower lobes and causing bullae

- Secondary membranoproliferative glomerulonephritis

- Cancer

- Hepatocellular carcinoma (liver)

- Bladder carcinoma

- Gallbladder cancer

- Lymphoma

- Lung cancer

People of Northern European and Iberian ancestry are at the highest risk for A1AD. Four percent carry the PiZ allele; between 1 in 625 and 1 in 2000 are homozygous.

Another study detected a frequency of 1 in 1550 individuals and a gene frequency of 0.026. The highest prevalence of the PiZZ variant was recorded in the northern and western European countries with mean gene frequency of 0.0140.

Hemolytic anemia affects nonhuman species as well as humans. It has been found, in a number of animal species, to result from specific triggers.

Some notable cases include hemolytic anemia found in black rhinos kept in captivity, with the disease, in one instance, affecting 20% of captive rhinos at a specific facility. The disease is also found in wild rhinos.

Dogs and cats differ slightly from humans in some details of their RBC composition and have altered susceptibility to damage, notably, increased susceptibility to oxidative damage from consumption of onion. Garlic is less toxic to dogs than onion.

Congenital malaria is an extremely rare condition which occurs due to transplacental transmission of maternal infection.

Clinical features include fever, irritability, feeding problems, anemia, hepatosplenomegaly and jaundice. Clinical features commence only after 3 weeks due to the protective effect of transplacentally transmitted antibodies.

Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of kernicterus.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, "Escherichia coli", and "Listeria monocytogenes" (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as "Streptococcus pneumoniae" and "Neisseria meningitidis". Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is sometimes used in neonatal sepsis. However, a 2009 study found that GM-CSF corrects neutropenia if present but it has no effect on reducing sepsis or improving survival.

Trials of probiotics for prevention of neonatal sepsis have generally been too small and statistically underpowered to detect any benefit, but a randomized controlled trial that enrolled 4,556 neonates in India reported that probiotics significantly reduced the risk of developing sepsis. The probiotic used in the trial was "Lactobacillus plantarum".

A very large meta-analysis investigated the effect of probiotics on preventing late-onset sepsis (LOS) in neonates. Probiotics were found to reduce the risk of LOS, but only in babies who were fed human milk exclusively. It is difficult to distinguish if the prevention was a result of the probiotic supplementation or if it was a result of the properties of human milk. It is also still unclear if probiotic administration reduces LOS risk in extremely low birth weight infants due to the limited number of studies that investigated it. Out of the 37 studies included in this systematic review, none indicated any safety problems related to the probiotics. It would be beneficial to clarify the relationship between probiotic supplementation and human milk for future studies in order to prevent late onset sepsis in neonates.

Newborns are relatively vitamin K deficient for a variety of reasons. They have low vitamin K stores at birth, vitamin K passes the placenta poorly, the levels of vitamin K in breast milk are low and the gut flora has not yet been developed (vitamin K is normally produced by intestinal bacteria).