The neonatal liver part II: Assessment and diagnosis of liver dysfunction

The liver, the largest organ in the body, performs many essential functions, including the storage and filtration of blood, production of bile, regulation of plasma proteins and glucose, and biotransformation of drugs and toxins. Many neonates display signs of hepatic dysfunction such as hyperbilirubinemia, hepatomegaly, or elevated liver enzymes. Primary liver disease in neonates is rare; much of the liver dysfunction seen in the neonatal period is secondary to systemic illness such as sepsis or hypoxic injury. It is important for the clinician to have the skills and knowledge necessary to distinguish intrinsic liver disease from liver dysfunction resulting from extrahepatic causes. Early intervention to address the cause of dysfunction is critical to successful management of liver disease. This article reviews the assessment of liver function in neonates and examines the techniques used to diagnose liver dysfunction.     

The neonatal liver, Part 1: embryology, anatomy, and physiology

The liver is the largest organ in the body and is critical to a number of metabolic, regulatory, and detoxification processes. These include the production of bile, metabolic processing of nutrients, synthesis and regulation of plasma proteins and glucose, and biotransformation of drugs and toxins.     

Pathophysiology of neonatal subconjunctival hemorrhage.

Of 111 newborns examined, 33 had subconjunctival hemorrhage (SCHN). Three of 19 patients delivered by cesarean section and 30 of 92 newborns delivered by the vaginal route had SCHN. Perinatal factors including duration of membrane rupture, length of second stage of labor, maternal weight and weight/length ratio, maternal ingestion of anti-inflammatory drugs, gravidity, birth weight, and Apgar score did not differ significantly in the groups with and without SCHN. It is proposed that in the majority of cases SCHN is a consequence of elevated venous pressure in the head and neck produced by compression of the fetal thorax and/or abdomen by uterine contractions. Tight umbilical cord around the neck probably represents an additional mechanism for SCHN.     

Pathophysiology of neonatal resuscitation: application in a global context

Despite the adoption of evidence-based guidelines for neonatal resuscitation, formulated with international consensus, the process of resuscitating a newly born infant remains a uniquely local activity. Variations in the physical environment, cultural and medical beliefs, and available resources mediate significant difference in practices worldwide. Yet, the universal nature of the physiology surrounding birth, and its disturbances, provides a common basis for reference. Recognition of the importance of assistance available at the moment of birth, management of the thermal environment, and establishment of adequate ventilation is nearly universal. Differences in specific practices arise from local differences in the risks and challenges to perinatal health, which, in turn, stem from the environment or the available resources. Valuable information can be learned through comparison and evaluation of different techniques. In such a way, the evidence base for neonatal resuscitation can be strengthened and infants around the world can share in the benefits realized.     

Pathophysiology of neonatal brain lesions: lessons from animal models of excitotoxicity

AIM: The pathophysiology of perinatal brain lesions is probably complex and multifactorial. The development and characterization of distinct yet complementary animal models should help to unravel the cellular and molecular mechanisms underlying perinatal brain lesions. This paper reviews experimental data obtained in animal models of neonatal excitotoxic brain lesions that closely mimic some of the lesions found in human cerebral palsy. CONCLUSION: Available data point to a key role for brain macrophages and oligodendrocytes in neonatal rodent excitotoxic brain lesions and underline the impact of cytokines on these lesions.     

Cardiac dysfunction in congenital diaphragmatic hernia: Pathophysiology,clinical assessment,and management

Cardiac dysfunction is an important consequence of pulmonary hypertension in congenital diaphragmatic hernia and a determinant of disease severity. Increased afterload leads to right ventricular dilatation and diastolic dysfunction. Septal displacement and dysfunction impair left ventricular function, which may also be compromised by fetal hypoplasia. Biventricular failure contributes to systemic hypotension and hypoperfusion. Early and regular echocardiographic assessment of cardiac function and pulmonary artery pressure can guide therapeutic decision-making, including choice and timing of pulmonary vasodilators, cardiotropes, ECMO, and surgery.     

The neonatal liver: Normal development and response to injury and disease

The liver emerges from the ventral foregut endoderm around 3 weeks in human and 1 week in mice after fertilization. The fetal liver works as a hematopoietic organ and then develops functions required for performing various metabolic reactions in late fetal and neonatal periods. In parallel with functional differentiation, the liver establishes three dimensional tissue structures. In particular, establishment of the bile excretion system consisting of bile canaliculi of hepatocytes and bile ducts of cholangiocytes is critical to maintain healthy tissue status. This is because hepatocytes produce bile as they functionally mature, and if allowed to remain within the liver tissue can lead to cytotoxicity. In this review, we focus on epithelial tissue morphogenesis in the perinatal period and cholestatic liver diseases caused by abnormal development of the biliary system.     

Transient left myocardial dysfunction: a cause of neonatal hypoxemia]

Refractory hypoxemia in the newborn requires an accurate diagnostic investigation for an optimal and prompt management. CASE REPORT: After a short delivery, a post-term newborn developed a severe hypoxemia with patchy pulmonary alveolar opacities and systolic right-to-left extrapulmonary shunting through the ductus arteriosus. Echocardiography ruled out a cardiac malformation and showed dilated left atrium with left-to-right shunting by the ovale foramen due to left ventricular dysfunction. Inotropic support associated with mechanical ventilation allowed a rapid improvement. CONCLUSION: A pathophysiological analysis is needed in case of severe neonatal hypoxemia. Doppler ultrasound is a non invasive and rapid method allowing the adjustment of the therapeutic strategy.     

Cardiovascular dysfunction in infants with neonatal encephalopathy

Severe perinatal asphyxia with hypoxic ischaemic encephalopathy occurs in approximately 1-2/1000 live births and is an important cause of cerebral palsy and associated neurological disabilities in children. Multiorgan dysfunction commonly occurs as part of the asphyxial episode, with cardiovascular dysfunction occurring in up to a third of infants. This narrative paper attempts to review the literature on the importance of early recognition of cardiac dysfunction using echocardiography and biomarkers such as troponin and brain type natriuretic peptide. These tools may allow accurate assessment of cardiac dysfunction and guide therapy to improve outcome.     

Spinal cord dysfunction in neonatal meningococcal meningitis

A 3-week-old infant with meningococcal meningitis is described whose clinical course was complicated by paraparesis and urinary retention. This rare complication of meningococcal meningitis has not previously been reported in the neonatal age group.     

Fetal and neonatal liver tumours

Liver tumours are rare in children and account for about 5% of all tumours in the fetus and newborn. The most frequently occurring are benign vascular tumours and mesenchymal hamartomas although malignancy in the form of hepatoblastoma is a possibility. While the diagnosis can be suspected antenatally (by ultrasound and MR scan), a precise diagnosis is often difficult due to the complexity of the tumours. Inutero development of such tumours may be associated with polyhydramnios, fetal hydrops and extreme cases the maternal mirror syndrome. Postnatal symptoms may include abdominal distension, cardiac failure, consumptive coagulopathy and bleeding due to tumour rupture, but is dependent on the nature of the actual tumour. Treatment options may include watchful waiting, surgical resection, hepatic artery embolisation/ligation and chemotherapy.     

Coeliac disease and liver dysfunction

The spectrum and pathogenesis of liver dysfunction in coeliac disease (CD) is reviewed. CD and liver disease share common risk factors, and consequences of CD may cause liver dysfunction. Liver dysfunction should be sought in CD, and its aetiology explored when abnormalities persist after gluten exclusion. CD should be excluded in patients with unexplained liver dysfunction before being labelled "cryptogenic".