| Neonatal infection | |
|---|---|
 | |
| 26-week gestation, premature infant, weighing <990gm with ventilator | |
| Specialty | Infectious disease,Pediatrics |
Neonatal infections are infections of theneonate (newborn) acquired duringprenatal development or within the first four weeks of life.[1] Neonatal infections may be contracted bymother to childtransmission, in thebirth canal duringchildbirth, or after birth.[2] Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such asHIV,hepatitis B, andmalaria do not become apparent until much later. Signs and symptoms of infection may includerespiratory 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) andpremature rupture of membranes (breakage of theamniotic sac) which substantially increases the risk ofneonatal sepsis by allowing passage for bacteria to enter the womb prior to the birth of the infant. Preterm orlow 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.[3]
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.[4]
Antibiotics can be effective for neonatal infections, especially when thepathogen 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 theneonatal intensive care unit (NICU). Neonatal infection can be distressing to the family and it initiates concentrated effort to treat it byclinicians. Research to improve treatment of infections and prophylactic treatment of the mother to avoid infections of the infant is ongoing.[5]
Signs and symptoms of infection include respiratory distress, temperature instability, irritability, failure to thrive, and skin rashes.[citation needed]
Early-onset sepsis (EOS), defined as onset of symptoms within 72 hours of life, is generally caused by transmission ofpathogens from thefemale genitourinary system to the fetus. Pathogens can infect the fetus viavertical transmission (direct transmission through the placenta in utero) or infection during delivery as fetus passes throughvaginal canal.[citation needed]
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.[3]
There are many etiologies of neonatal infection, including bacterial, viral and fungal pathogens. The source of infectiousbacteria and other pathogens is often thematernalgastrointestinal andgenitourinary tract. Many of the maternal infections with these organisms areasymptomatic in the mother. Other maternal infections that may be transmitted to the infant inutero or during birth are bacterial and viralsexually transmitted infections. The infant's ability to resist infection is limited by its immatureimmune system. In addition, the immune system of the neonate may respond in ways that can create problems that complicate treatment, such as the release ofinflammatory chemicals. Congenital defects of the immune system also affect the infants ability to fight off the infection.[6]
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 togram-positive bacteria andcoagulase positive staphylococci.[7] ...
Group B streptococcus (GBS), also namedStreptococcus 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 isvertically 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).[8]
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-resistantEscherichia 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.[9]
Neisseria gonorrhoeae is a commonsexually transmitted infection 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 ofpreterm delivery. The most common manifestation of gonococcal infection in a newborn isneonatal conjunctivitis, an infection of the eyes that presents with green-yellowexudate and eyelid swelling. Without treatment, this infection can lead to permanentvisual impairment. Treatment ofNeisseria gonorrhoeae conjunctivitis consists of a single dose ofceftriaxone (antibiotic). Typically, all neonates (regardless of symptoms or risk factors) receiveerythromycin ointment applied to both eyes after delivery[10]
Listeria monocytogenes is a gram-positive bacilli that can cause infection acquired fromtainted food and present in the mother. The presence of this pathogen can sometimes be determined by the symptoms that appear as agastrointestinal illness in the mother. The mother acquires infection from ingesting food that containsanimal products such ashot dogs,unpasteurizedmilk,delicatessen meats, andcheese.[11]
Clostridium tetani can cause a generalised form oftetanus 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.[12]
Less common bacterial pathogens includeStreptococcus pyogenes,Viridans streptococci,Streptococcus pneumoniae,Haemophilus influenzae, andPseudomonas aeruginosa.[13][citation needed]
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:
Symptoms of HIV in a child will vary depending on the age of presentation. Common symptoms includefailure to thrive, recurrent infections such aspneumonia, intermittent diarrhea, swollen lymph nodes andoral 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.[15]
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 andretinitis. Long-term complications of congenital CMV infections may includesensorineural hearing loss,developmental delay, and seizures. Due to high prevalence of disease, CMV is not routinely screened in pregnant patients.[16]
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:
Maternal infection withrubella virus during pregnancy can lead tocongenital 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 includecataracts,hearing impairment,developmental delay andcongenital heart disease.[18]
Zika virus is an arthropod-borne virus transmitted bymosquitos, and infection during pregnancy can lead to severe congenital abnormalities in a newborn. Congenital infection can lead tofetal growth restriction and CNS abnormalities, includingmicrocephaly,ventriculomegaly and intracranial calcifications.[19]
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.[20]
Other viral infections, such asrespiratory syncytial virus (RSV),metapneumovirus (hMPV),rhinovirus,parainfluenza (PIV), andhuman coronavirus in the neonatal period are associated with recurrentwheezing in later childhood.[citation needed]
In very low birth weight infants (VLBWI), systemic fungus infection is ahospital-acquired infection with serious consequences. The pathogens are usuallyCandida albicans andCandida parapsilosis. A small percentage of fungal infections are caused byAspergillus,Zygomycetes,Malassezia, andTrichosporon.[22][23] Infection is usually late-onset. Up to 9% of VLBWI with birth weights of <1,000 g develop these fungus infections leading to sepsis or meningitis. As many as one-third of these infants can die. Candidiasis is associated with retinopathy, prematurity and negative neurodevelopmental consequences. Candida can colonize the gastrointestinal tract of low birthweight infants (LBI). This gastrointestinal colonization is often a precursor to a more serious invasive infection. The risk of serious candida infection increases when multiple factors are present. These are:thrombocytopenia, the presence of candidal dermatitis, the use of systemic steroids, birth weights of <1,000 g, presence of a central catheter, postponing enteral feeding, vaginal delivery, and the amount of time broad-spectrum antibiotics were given.[23]
Infants born withmalaria can be infected with a variety ofspecies;Plasmodium vivax,Plasmodium malariae,Plasmodium ovale, andPlasmodium falciparum. In most instances of congenital malaria is caused byP. vivax andP. falciparum. Women living in areas where malaria is prevalent and common are repeatedly exposed to malaria. In response to maternal infection, mothers develop antimalarialantibodies. It is probable that the antibodies present in the mother offers protection for the baby. Bacterial infection can develop with malaria.[22]
Infants that are infected by the protozoanToxoplasma gondii in utero can be born withchorioretinitis or ocular toxoplasmosis. Globally, it is the most common cause of infections of the back of the eye. (posterior segment). The most common sign is decreased vision in one eye. Other signs and symptoms may appear after the neonatal period and include: chorioretinitis development later in life, intracranial calcification hydrocephalus or central nervous system abnormalities.[24]
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.[citation needed]
Maternal risk factors for neonatal infection include:
Inflammation accompanies infection and is likely to complicatetreatment and recovery. Inflammation is linked to reduced growth of thelungs of the premature baby.[26]
The recent identification of the presence ofmicroorganisms in maternal-infant body fluids that were previously thought to be sterile has provided one explanation for the presence of the inflammatory response in both the mother and infant. Sixty-one percent of pregnant women withchorioamnionitis, or inflammation of theamniotic fluid, were found to be infected by microorganisms. Often,more than one pathogen was present. In fifteen percent of pregnant women inflammation was still evident even though there was no evidence of pathogens. This may indicate that there are other causes. A high percentage, 51% to 62%, of pregnant women who had chorioamnionitis also had inflammation of theplacenta.[26]
Diagnosis of infection is based upon the recovery of the pathogen or pathogens from the typicallysterile sites in the mother or the baby. Unfortunately, as many half of pregnant women are asymptomatic with a gonorrhea infection and other sexually transmitted infections.[27][28][29] Samples are obtained fromurine,blood orcerebrospinal fluid. Diagnosis of infection can also be aided by the use of more nonspecific tests such as determining the totalwhite blood cell count,cytokine levels and other blood tests andsigns.[30]
| Signs of infection | Notes | References |
|---|---|---|
| abnormalcomplete blood count | looking for signs of infection in the blood: increased white cell count; presence of immature neutrophils | [31][32] |
| increased C-reactive protein | a chemical in the blood that shows that the baby's immune system is actively reacting to infection | [31][32][33] |
| accessory muscle use | using the intercostal muscles to assist in breathing | [32] |
| tachycardia | aheart rate that is faster than normal | [31] |
| bradycardia | a heart rate that is slower than normal | [31] |
| chest recession | [32] | |
| respiratory distress | the baby has trouble breathing | [31][32] |
| nasal flaring | the baby's nostrils expand when it inhales | [32] |
| expiratory grunt | a sound of effort when the baby exhales | [32][34] |
| apnea | the baby stops breathing | [31][32] |
| rash | [32] | |
| positive urine culture | [31] | |
| positive cerebral spinal fluid | [31] | |
| other positive cultures | from eyes, ear canal, umbilicus axilla anus | [31] |
| lethargy | the baby seems tired and has slow or no movements | [31][32] |
| hypotonia | the muscles seem flabby and weak | [31][32] |
| hypothermia | [31] | |
| irritability | infant appears uncomfortable and has difficulty being soothed | [31][32] |
| weak cry | [32] | |
| pneumonia | [31] | |
| poor perfusion | poor circulation | [31][32] |
| hypotension | low blood pressure | [32] |
| acidosis | pH imbalance in the blood | [31][32] |
| diarrhea | water-like, unformed stools | [32] |
| poor feeding | [31] | |
| oxygen requirement | [31] | |
| bulgingfontanel | the soft spot on the head is bulging | [32] |
| seizures | [31][32] | |
| fever | [31] | |
| disseminated intravascular coagulation | widespread clotting of blood | [32] |
| kidney failure | kidneys do not function | [32] |
| bacteremia | bacteria cultured from the blood of the newborn | [31] |
Symptoms and the isolation of the virus pathogen the upper respiratory tract is diagnostic. Virus identification is specific immunologic methods and PCR. The presence of the virus can be rapidly confirmed by the detection of the virus antigen. The methods and materials used for identifying the RSV virus has a specificity and sensitivity approaching 85% to 95%. Not all studies confirm this sensitivity. Antigen detection has comparatively lower sensitivity rates that approach 65% to 75%.[35]
Congenital malaria has its own set of signs:
| Signs of congenital malaria infection | Notes | References |
|---|---|---|
| splenomegaly | enlarged speen | |
| fever | ||
| anemia | ||
| jaundice | ||
| poor feeding | ||
| hepatomegaly | enlarged liver | |
| failure to thrive | ||
| loose stools | ||
| irritability | ||
| hyperbilirubinemia | ||
| central nervous system infection | ||
| splenic rupture | ||
| kidney failure | ||
| blackwater fever | infection with P. falciparum only | [22] |
Neonatal sepsis of the newborn is an infection that has spread through the entire body. The inflammatory response to this systematic infection can be as serious as the infection itself.[26] In infants that weigh under 1500 g,sepsis is the most common cause of death. Three to four percent of infants per 1000 births contract sepsis. The mortality rate from sepsis is near 25%.[36] Infected sepsis in an infant can be identified by culturing the blood and spinal fluid and if suspected, intravenous antibiotics are usually started. Lumbar puncture is controversial because in some cases it has found not to be necessary while concurrently, without it estimates of missing up to one third of infants with meningitis is predicted.[30]
To reduce neonatal infection, screening of pregnant women for HIV, hepatitis B, and syphilis, is available in the UK and the United States.[37][38]
Treatment with a vaginal antibiotic wash prior to birth does not prevent infection with group B streptococcus bacteria (GBS).[31][39] Treatment with vaginal chlorhexidine prior to birth does not prevent neonatal infections.[40]
Because GBS bacteria can colonize the lower reproductive tract of 30% of women, typically pregnant women are tested for this pathogen from 35 to 37 weeks of pregnancy. Before delivery treatment of the mother with antibiotics reduces the rate of neonatal infection.[31] Prevention of the infection of the baby is done by treating the mother with penicillin. Since the adoption of this prophylactic treatment, infant mortality from GBS infection has decreased by 80%.[36]
Mothers with symptomaticgenital herpes and who are treated with antiviral prophylaxis are less prone to have an active, symptomatic case at the time of birth and it may be able to reduce the risk of passing on HSV during birth. Cesarean delivery reduces the risk of infection of the infant.[41]
Breastfeeding has been shown to protect the neonate from some infections.[42][43][44][45][46][excessive citations] Breast milk protects against necrotizingenterocolitis.[47]
Hepatitis A, B, and D are preventable via vaccination. Hepatitis A can be prevented by immunization against HAV, while Hepatitis B and D can both be prevented by immunization against HBV.[20]
The Hepatitis B vaccination is among the first two injections a newborn receives.[48] The other is vitamin K to preventvitamin K deficiency bleeding.[49] In cases where the pregnant woman is positive for hepatitis B, the baby will receive an additional dose of hepatitis B immunoglobulin in addition to the hepatitis B vaccine to prevent transmission of the disease from mother to baby.[50] Prevention of hepatitis B is crucial as there is no currently no cure.[51]
In general, in an unvaccinated individual, the viral hepatitis family causes liver damage due to a cell-mediated response via cytotoxic lymphocytes.[52] Acute viral hepatitis can lead to jaundice, elevated bilirubin, elevated liver enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase), and flu-like symptoms.[52] Importantly, acute neonatal HBV infections progress to chronic Hepatitis B about 90% of the time.[53] For both Hepatitis B and Hepatitis D, the most significant long-term complications are progression to cirrhosis and hepatocellular carcinoma, which carries high morbidity and mortality.[54]
Neonatal infection treatment is typically started before the diagnosis of the cause can be confirmed.Neonatal infection can be prophylactically treated with antibiotics.[55] Maternal treatment with antibiotics is primarily used to protect against group B streptococcus.[30]
Women with a history ofgenital herpes, can be treated with antiviral drugs to prevent symptomatic lesions and viral shedding that could infect the infant at birth. The antiviral medications used include acyclovir, penciclovir, valacyclovir, and famciclovir. Only very small amounts of the drug can be detected in the fetus. There are no increases in drug-related abnormalities in the infant that could be attributed to acyclovir. Long-term effects of antiviral medications have not been evaluated for their effects after growth and development of the child occurs. Neutropenia can be a complication of acyclovir treatment of neonatal HSV infection, but is usually transient.[41] Treatment with immunoglobulin therapy has not been proven to be effective and is not recommended.[56]
Up to 3.3 million newborns die each year and 23.4% of these die of neonatal infection. About half of the deaths caused by sepsis or pneumonia happen in the first week postpartum. In industrialized countries, prophylactic antibiotic treatment of the mothers identified with group B streptococcus, early identification of sepsis in the newborn, and administration of antibiotics to the newborn has reduced mortality.[31] Neonatal herpes in North America is estimated to be from 5 – 80 per 100,000 live births. HSV has a lower prevalence in mothers outside the United States. In the United Kingdom the incidence is much lower and estimated to be 1.6 per 100,000 live births. Approximately 70% to 80% of infected infants are born to mothers with no reported history of HSV infection.[41]
Regions with low neonatal mortality include Europe, the Western Pacific, and the Americas, which have sepsis rates that account for 9.1% to 15.3% of the total neonatal deaths worldwide. This is in contrast with the 22.5 to 27.2% percentage of total deaths in resource-poor countries such as Nigeria, the Democratic Republic of the Congo, India, Pakistan, and China.[31]
In the UK, the proportions of pregnant women who are newly screened positive for hepatitis B, syphilis, and HIV have remained constant since 2010 at about 0.4%, 0.14% and 0.15%, respectively. Estimated prevalence levels among pregnant women for hepatitis B and HIV, including previous diagnoses, were higher at 0.67% and 0.27%. Pregnant women evaluated as susceptible to rubella due to low antibody levels have increased by over 60%, to about 7.2%. However, this increase is probably due to changes in testing methods and evaluation criteria.[57]
In North America, prior to the 1950s, group A β-hemolytic streptococcus (GAS) was the most common pathogen associated with neonatal sepsis prior to the 1960s. In the past twenty years, the most common pathogen causing sepsis is coagulase-negative staphylococci that exist as biofilms associated with infected central venous or arterial catheters.[55] Infections can be fatal and contribute to long-term morbidity and disability among the infants who survive into childhood.[55] Neonatal sepsis effects 128 cases per 1000 live births. Meningitis can occur in the septic infant.[30]Expectant mothers with HSV have a 75% chance of at least one flare-up during their pregnancy.[41] In limited studies it was found that infants in Africa born to mothers with malaria have a 7% of acquiring congenital malaria.[22]
Early onset sepsis can occur in the first week of life. It usually is apparent on the first day after birth. This type of infection is usually acquired before the birth of the infant.Premature rupture of membranes and otherobstetrical complications can add to the risk of early-onset sepsis. If the amniotic membrane has been ruptured greater than 18 hours before delivery the infant may be at more risk for this complication. Prematurity, low birth weight, chorioamnionitis, maternal urinary tract infection and/or maternal fever are complications that increase the risk for early-onset sepsis. Early onset sepsis is indicated by serious respiratory symptoms. The infant usually develops pneumonia, hypothermia, or shock. The mortality rate is 30 to 50%.[30]
Infections that occur after the first week of life but before the age of 30 days are considered late onset infections. Obstetrical and maternal complications are not typically the cause of these late onset infections; they are usually acquired by the infant in the hospital neonatal intensive care unit. The widespread use of broad-spectrum antibiotics in the nursery intensive care unit can cause a higher prevalence of invasive antibiotic resistant bacteria.[30] Meconium aspiration syndrome has a mortality rate just over 4%. This accounts for 2% for all neonatal deaths.[58]
The susceptibility to risk of infection and immune deficiencies are active areas of research. Studies regarding the role of viruses in neonatal infections are lacking. Research also continues into the role and protective effect of gut, skin and other human microbiomes and the colonization during the neonatal period.[26][30] The comparison between both resource rich and poor countries makes it difficult to compare the diagnosis success; as industrialized regions are able to confirm the diagnosis and presence of pathogens in the clinical laboratory. Clinical testing may not be available in all settings and clinicians must rely on the signs of infection in the newborn. Research data from Africa and Southeast Asia is scarce.[31]
The result of some research has been the identification of diagnostic tools and procedures that could identify mothers with group B streptococcus infection in resource-poor regions. These procedures would be easy and inexpensive to use. Those mothers who are identified as being infected could then be prophylactly treated prior to the birth of the baby.[31]
Probiotic administration of Lactobacillus species has shown some success.[59]
A GBS vaccine is currently being tested but not currently available. Vaccination is estimated to being able to prevent 4% of GBS infections for preterm births and 60–70% for neonatal GBS infections in the US. The projected benefits of maternal vaccination is the prevention of 899 cases of GBS disease and 35 deaths among infants. The cost savings in the prevention of GBS may be over 43 million dollars. Vaccination may be especially beneficial in low to middle income countries where screening and prophylactic treatment is not possible. Analysts project that GBS vaccination would prevent 30–54% of infant GBS cases. Screening, prophylactic antibiotics and vaccine would prevent 48% of infection.[60]
Pregnant women and their newborns are much more likely to get a Listeria infection, which is called listeriosis.
NT most often occurs through cutting of the umbilical cord using non-sterile techniques or applying non-sterile traditional remedies to the umbilical cord stump, but infection of the umbilical stump is not always evident. Deliveries carried out by persons with unclean hands or on a contaminated surface are also risk factors for maternal and neonatal tetanus (MNT).
The organisms and pathogens that are most associated with neonatal sepsis differ depending upon country involved. Pathogens range from gram positive and negative bacteria to viruses and fungi, with bacteria being the most frequently identified. The most commonly implicated bacteria includeStaphylococcus aureus, coagulase negative staphylococci (CONS),Streptococcus pneumoniae,Streptococcus pyogenes,Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa,Salmonella typhi, and Group B streptococcus (GBS)
