User:Ryanparnell/Neonatal infection

Neonatal infection

Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or within the first four weeks of life. Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or after birth. Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later. Signs and symptoms of infection may include respiratory distress, temperature instability, irritability, poor feeding, failure to thrive, persistent crying and skin rashes.

Risk factors include previous maternal infection, preterm delivery (< 37 weeks gestation) and premature rupture of membranes (breakage of the amniotic sac) which substantially increases the risk of neonatal sepsis by allowing passage for bacteria to enter the womb prior to the birth of the infant. Preterm or low birth weight neonates are more vulnerable to neonatal infection. While preterm neonates are at a particularly high risk, all neonates can develop infection. Maternal screening for intrapartum infections reduce the risk of neonatal infection. Pregnant women may receive intrapartum antibiotic prophylaxis for prevention of neonatal infection.

Infant respiratory distress syndrome is a common complication of neonatal infection, a condition that causes difficulty breathing in preterm neonates. Respiratory distress syndrome can arise following neonatal infection, and this syndrome may have long-term negative consequences. In some instances, neonatal respiratory tract diseases may increase the susceptibility to future respiratory infections and inflammatory responses related to lung disease.

Antibiotics can be effective for neonatal infections, especially when the pathogen is quickly identified. Instead of relying solely on culturing techniques, pathogen identification has improved substantially with advancing technology; however, neonate mortality reduction has not kept pace. In industrialized countries, treatment for neonatal infections takes place in the neonatal intensive care unit (NICU). Neonatal infection can be distressing to the family and it initiates concentrated effort to treat it by clinicians. Research to improve treatment of infections and prophylactic treatment of the mother to avoid infections of the infant is ongoing.

Etiologies

Early-onset sepsis (EOS), defined as onset of symptoms within 72 hours of life, is generally caused by transmission of pathogens from the female genitourinary system to the fetus. Pathogens can infect the fetus via vertical transmission (direct transmission through the placenta in utero) or infection during delivery as fetus passes through vaginal canal.

Late-onset sepsis (LOS), defined as onset of symptoms after 72 hours of life, is generally caused by transmission of pathogens from the environment after delivery. Infants requiring intravascular catheters and other invasive procedures are at increased risk for developing LOS.

There are many etiologies of neonatal infection, including bacterial, viral and fungal pathogens. The source of infectious bacteria and other pathogens is often the maternal gastrointestinal and genitourinary tract. Many of the maternal infections with these organisms are asymptomatic in the mother. Other maternal infections that may be transmitted to the infant in utero or during birth are bacterial and viral sexually transmitted infections. The infant's ability to resist infection is limited by its immature immune system. In addition, the immune system of the neonate may respond in ways that can create problems that complicate treatment, such as the release of inflammatory chemicals. Congenital defects of the immune system also affect the infants ability to fight off the infection.

Bacteria

Bacteria found in the maternal gastrointestinal or gastrourinary tracts can commonly lead to neonatal infection. Bacterial infections may present as fetal distress at birth (including signs of tachycardia, temperature instability or difficulty breathing), neonatal sepsis, or neonatal meningitis. Infections that develop during NICU admissions are more commonly coagulase-negative staphylococci, especially in infants with indwelling catheters. Infections that develop one month after the birth of the infant are more likely due to Gram-positive bacteria and coagulase positive staphylococci.

Group B Streptococcus (GBS)

Group B streptococcus (GBS), also named Streptococcus agalactiae, is a bacteria typically identified as the cause of the majority of early-onset infections in the neonate. GBS is an encapsulated gram-positive cocci that colonizes the gastrointestinal and genital tracts of pregnant women. Maternal infections are usually asymptomatic. This pathogen is vertically transmitted (transmitted directly from the mother's vagina into the infant's amniotic fluid after onset of labor). Due to the high prevalence of GBS, routine screening for the bacteria occurs during pregnancy. If the bacteria is found in the maternal GI / GU tract, mothers will receive IV antibiotic (usually penicillin or ampicillin).

Escherichia coli (E. coli)

Escherichia coli is an encapsulated gram-negative bacilli that may cause neonatal infections due to its high prevalence in the GI and GU tracts of pregnant patients. With the advances in preventing group B streptococcus infections, β-lactam-resistant Escherichia coli infections have increased in causing neonatal deaths in very low birthweight and premature infants. Common complications of neonatal E.coli infection include neonatal sepsis and neonatal meningitis.

Neisseria gonorrhoeae

Neisseria gonorrhoeae is a common sexually transmitted disease which may be present in pregnant women at time of delivery. This pathogen is usually acquired during delivery, occurring in 30-40% of cases with known maternal infection. Additionally, untreated maternal gonorrhea may increase the risk of preterm delivery. The most common manifestation of gonococcal infection in a newborn is neonatal conjunctivitis, an infection of the eyes that presents with green-yellow exudate and eyelid swelling. Without treatment, this infection can lead to permanent visual impairment. Treatment of Neisseria gonorrhoeae conjunctivitis consists of a single dose of ceftriaxone (antibiotic). Typically, all neonates (regardless of symptoms or risk factors) receive erythromycin ointment applied to both eyes after delivery

Listeria monocytogenes

Listeria monocytogenes is a gram-positive bacilli that can cause infection acquired from tainted food and present in the mother. The presence of this pathogen can sometimes be determined by the symptoms that appear as a gastrointestinal illness in the mother. The mother acquires infection from ingesting food that contains animal products such as hot dogs, unpasteurized milk, delicatessen meats, and cheese.

Clostridium tetani

Clostridium tetani can cause a generalised form of tetanus in the neonate. This usually occurs when the mother has not been vaccinated against tetanus and the baby has not acquired passive immunity. The umbilical cord region is the most susceptible.

Other Bacterial Pathogens

Less common bacterial pathogens include Streptococcus pyogenes, Viridans streptococci, Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa.

Viruses

Human Immunodeficiency Virus (HIV)

Human immunodeficiency virus (HIV) infection can occur during delivery of the neonate, in utero through mother-to-child transmission or postnatally by way of breastfeeding. Most transmission occurs during delivery. Transmission depends on multiple risk factors, usually centered around the viral load of HIV in the mother. Strategies for reducing transmission of HIV include:

• Anti-retroviral therapy during pregnancy, reducing amount of HIV virus in the maternal bloodstream
• Delivery by Caesarean section in mothers with plasma viral load > 1000 copies / mL
• Using prophylactic anti-retroviral therapy in the newborn infant, especially in mothers with high viral loads
• Avoiding breast-feeding

Symptoms of HIV in a child will vary depending on the age of presentation. Common symptoms include failure to thrive, recurrent infections such as pneumonia, intermittent diarrhea, swollen lymph nodes and oral thrush. In infants, diagnostic testing for HIV relies of detection of the virus in the bloodstream. For infants born to HIV-infected mothers, diagnostic testing will be performed within days of delivery, at 1-2 months and at 4-6 months of age.

Cytomegalovirus (CMV)

Cytomegalovirus (CMV) is the most common congenital viral infection, usually transmitted through the placenta during pregnancy. Most neonates with congenital CMV infection will not have any symptoms, but a minority of infected newborns will have symptomatic infection. Common symptoms include rash, microcephaly (small head), low birth weight, jaundice, thrombocytopenia, seizures and retinitis. Long-term complications of congenital CMV infections may include sensorineural hearing loss, developmental delay, and seizures. Due to high prevalence of disease, CMV is not routinely screened in pregnant patients.

Herpes Simplex Virus (HSV)

Herpes simplex virus (HSV), which commonly causes cold sores and painful genital blisters can cause congenital infection via direct contact with genital tract lesions during delivery. Neonatal HSV may be classified into three categories based on symptom presentation:

• Localized skin, eye and mouth disease - 35-45% of neonatal HSV infections. Presentation includes clustering vesicular lesions with erythematous base in localized area of skin which can spread to the eye or oropharynx. There is risk of progression to CNS or disseminated disease, so infants should be thoroughly evaluated for progression of symptoms.
• CNS disease - 30% of neonatal HSV infections. HSV spreads into the brain, leading to seizures, lethargy, irritability, poor feeding, temperature instability within the first six weeks of life. Diagnosis of CNS disease can be made with cerebrospinal fluid analysis or electroencephalogram (EEG) showing lateralized periodic discharges. It can be difficult to distinguish between HSV CNS disease and other causes of neonatal meningitis; therefore, it is recommended to start empiric acyclovir in all cases of neonatal meningitis.
• Disseminated disease - 25-30% of neonatal HSV infections. Disease is defined by multi-organ involvement, including liver, lungs CNS, heart, kidney, GI tract, and skin. Neonates with disseminated HSV infection present with nonspecific symptoms of neonatal sepsis. All infants with signs of neonatal sepsis should undergo testing for HSV and empiric antiviral therapy.

Hepatitis

There are five liver specific viruses (hepatitis A, B, C, D, E) that could potentially harm the mother and child. Acute hepatitis A virus or acute hepatitis E virus infection present the greatest risk to maternal and fetal health and increased risk of adverse pregnancy outcomes. Hepatitis B, C and D virus present a risk of mother to child transmission but are dependent on the severity of the underlying disease in the mother. However, hepatitis B virus is the major cause of neonatal infection.

• Hepatitis A is a non-enveloped, single-stranded RNA virus that is spread through the fecal-oral route with the main modes of transmission being close personal contact or ingestion of contaminated food or water. During pregnancy, hepatitis A can cause placental abruption, premature rupture of membranes, and increased rates of preterm labor.
• Hepatitis B is an enveloped, double stranded DNA virus that is spread by exposure to blood, with the main modes of transmission are blood, sexual transmission, or perinatal. During pregnancy, acute hepatitis B infection can result in increased risk of preterm delivery, low birth weight and increased risk of gestational diabetes mellitus. Chronic hepatitis B infection is the largest concern globally. Chronic hepatitis B infection can lead to acute liver failure and increased alanine aminotransferase flares. There is also an increased risk of mother to child transmission and occurs during the delivery of the neonate from an infected mother. Some infected neonates will develop acute hepatitis B and symptomatically will develop abdominal distension, jaundice, clay- colored stools and failure to thrive. However, most infected neonates will be asymptomatic but will chronically have persistent hepatitis B surface antigens in the blood and elevated transaminase levels.
• Hepatitis C is an enveloped, single stranded RNA virus that is spread by exposure to blood, with the main modes of transmission are blood, sexual transmission, or perinatal. Chronic infection with hepatitis C virus may influence pregnancy outcomes, such as increased rates of small for gestational age, intrauterine death, low birthweight, and preterm delivery, but no clear association between these adverse outcomes and hepatitis C infection have been observed. There is also an increased risk of mother to child transmission and is largely attributable to events during the birth process.
• Hepatitis D is a single stranded RNA virus that is spread by exposure to blood, with the main modes of transmission are blood, sexual transmission, or perinatal. There is limited research on the effects of hepatitis D infection on fetal or infant outcomes, but the effects are thought to be similar to those with hepatitis B infection.
• Hepatitis E is a non-enveloped, single stranded RNA virus that is spread through the fecal-oral route with the main modes of transmission being close personal contact or ingestion of contaminated food or water. During pregnancy, acute hepatitis E infections result in an increase in adverse pregnancy outcomes such as increased maternal and fetal morbidity and mortality, acute hepatic failure, and associated complications with preterm birth.

Rubella

Maternal infection with rubella virus during pregnancy can lead to congenital rubella syndrome. The risk of congenital infection is highest during the first trimester (< 12 weeks). Risk of congenital rubella is increased among immigrant women from countries without adequate vaccination programs. Common symptoms include cataracts, hearing impairment, developmental delay and congenital heart disease.

Zika

Zika virus is an arthropod-borne virus transmitted by mosquitos, and infection during pregnancy can lead to severe congenital abnormalities in a newborn. Congenital infection can lead to fetal growth restriction and CNS abnormalities, including microcephaly, ventriculomegaly and intracranial calcifications.

Other Viral Pathogens

Other viral infections, such as respiratory syncytial virus (RSV), metapneumovirus (hMPV), rhinovirus, parainfluenza (PIV), and human coronavirus in the neonatal period are associated with recurrent wheezing in later childhood.

Risk Factors

Preterm neonates are at greater risk of infection, including severe complications such as sepsis and meningitis. Preterm neonates usually have ineffective immune systems, due to decreased IgG antibodies and decreased complement activation. Additionally, preterm neonates require longer hospital admissions, including the placement of invasive devices that increase risk of infection.

Maternal risk factors for neonatal infection include:

• Chorioamnionitis - acute inflammation of amniotic fluid and fetal membranes during pregnancy, usually caused by polymicrobial bacterial infection. Signs of infection include maternal fever, vaginal discharge, tender uterus or pain with urination.
• GBS Colonization - group B streptococcus is a bacterial pathogen commonly found in the gastrointestinal and vaginal membranes of healthy women. Presence of this bacteria is usually asymptomatic; therefore, pregnant patients will routinely be screened for presence of GBS prior to delivery.
• Delivery Before 37 Weeks - premature infants require more medical intervention and have less effective immune defenses, so these neonates are at increased risk of infection
• Prolonged Rupture of Membranes (PROM) - the amount of time between the rupture of amniotic membranes and delivery of the neonate is directly correlated with risk of neonatal infection. Prolonged course of labor increases neonatal exposure to bacterial and viral pathogens, increasing chance of infection.