Neonatal Meningitis

What is Neonatal Meningitis?

Meningitis in newborns can lead to severe long-term consequences. Despite medical advancements, bacterial meningitis still results in unfavorable outcomes in 20 to 60% of survivors. Even with mortality rates decreasing over the years, diagnosing this condition remains difficult. This is partly due to the fact that the germs causing this disease can vary based on the baby’s gestational age at birth, age at presentation, and where they live. Also, symptoms can often be subtle and not the same in every baby. In addition, the use of antibiotics before analyzing cerebrospinal fluid (fluid around the brain and spinal cord) can lead to unclear test results, and special tests for virus-related meningitis are often not available. Due to these reasons, it is believed that the actual number of cases could be much higher than reported.

Newborns, especially those born prematurely, are at high risk for bacterial meningitis due to their immature immune system. Their exposure to various germs during birth also introduces risks for unique bacterial and viral infections, with the main culprits being group B streptococcus, gram-negative rods (a type of bacteria), with E. coli being the most common, and Listeria monocytogenes (another type of bacteria). However, infections caused by fungi and viruses should also be considered during diagnosis and treatment. Therefore, some experts recommend performing a lumbar puncture (a procedure in which fluid is taken from the spine for testing) on all babies with confirmed or suspected sepsis (a life-threatening condition caused by the body’s response to an infection) to rule out neonatal meningitis, aiming to diagnose and treat the disease early.

What Causes Neonatal Meningitis?

Meningitis in newborns can be caused by various pathogens, which can depend on a number of factors such as the baby’s birth gestational age, the baby’s age when they show symptoms, and where they’re located in the world. This disease can show up early (within the first 72 hours of life) or late (over 72 hours after birth). Late-onset meningitis is mostly seen in premature babies, particularly those in intensive care. The pathogens causing the disease can vary depending on whether the infection was caught in the hospital or in the community.

Bacterial and fungal causes of meningitis are more common in babies who were born preterm, have very low birth weight, experienced a premature or long-lasting rupture of membranes, or whose mothers had a certain type of bacteria called Group B Streptococcus or S. agalactiae. Early-onset meningitis has been greatly reduced thanks to antibiotics used during childbirth for Group B Streptococcus infection, but this infection is still the most common cause of meningitis and neonatal sepsis, accounting for over 40% of all early-onset infections. Other common bacteria causing early-onset meningitis include E. coli, Listeria monocytogenes, Enterococcus sp, and Streptococcus pneumoniae.

In cases of late-onset meningitis, the causes could be related to the baby’s gestational age at birth, their weight at birth, and whether the infection was caught in the community or a hospital. Group B Streptococcus and E. coli remain the most common causes of community-acquired late-onset meningitis. For those in hospital or intensive care at the time of the infection, the most common pathogens are coagulase-negative staphylococci and Staphylococcus aureus, followed by E. coli and Klebsiella pneumoniae. One needs to consider additional organisms like P. aeruginosa and methicillin-resistant S aureus when deciding what antibiotics to use in the hospital setting. Late-onset meningitis occurs more often as a complication of neonatal sepsis than in other periods.

Some studies have shown a shift from Group B Streptococcus to E. coli as the most common cause of neonatal meningitis in recent years. Other significant diseases causing neonatal meningitis include Candida sp and Cronobacter sakazakii, with the latter primarily found in new-born babies who have been fed powdered formulas. Meningitis in these babies often leads to further complications like brain abscesses, subdural empyemas, and hydrocephalus, leading to a high mortality rate. If meningitis is caused by Citrobacter sp, there might be a high rate of brain abscesses, which may cause more problems and deaths in the central nervous system.

It is essential to remember that babies exposed to HIV, even if they are not infected, are at a higher risk of bacterial infections, including those caused by Group B Streptococcus. Babies with indwelling vascular catheters, ventricular shunts and reservoirs, and endotracheal tubes are also at a higher risk of meningitis due to bacterial spread through blood or cerebrospinal fluid.

If the baby tests negative for bacterial meningitis but shows abnormal cerebrospinal fluid profiles, they might have viral meningitis. Although rare, some viral infections can cause meningitis in newborns including the enterovirus, human parechovirus type 3, and herpes simplex virus. Even more rare, viruses such as West Nile virus and Chikungunya can cause meningitis and meningoencephalitis in newborns.

Risk Factors and Frequency for Neonatal Meningitis

Bacterial and viral meningitis are conditions that can affect newborn babies. In the United Kingdom, research shows that each year, out of 1000 live births, around 0.38 babies will develop bacterial meningitis and about 0.83 will get viral meningitis. However, this might not be the full picture as only about 30-50% of babies in neonatal intensive care are tested for sepsis, and 75% of the testing is done after the babies are already on antibiotics, which can make the test results misleadingly negative.

In Canada, a study found that among 1000 admissions to neonatal intensive care, between 2.2 and 3.5 cases of meningitis were reported over seven years.

The incidence of bacterial and viral meningitis is 0.38 and 0.83 per 1000 live births, respectively, in the UK.
Not all babies in neonatal intensive care units are tested for sepsis, potentially leading to underreporting of meningitis cases.
In Canada, there are 2.2 to 3.5 cases of meningitis for every 1000 neonatal intensive care admissions over seven years.

The situation is even more serious in developing countries, where for every 1000 live births, between 0.8 and 6.1 babies will develop meningitis and up to 58% of them will not survive. However, the real number might be higher, especially in rural areas of developing countries, as many cases are likely not recorded.

In developing countries, meningitis affects between 0.8 and 6.1 per 1000 live births.
The mortality rate can be as high as 58%.
The actual frequency of meningitis cases could be higher, especially in rural areas.

Signs and Symptoms of Neonatal Meningitis

The symptoms of meningitis can differ greatly depending on the weight and age of the newborn. Some of the common symptoms include seizures, a swollen soft spot on the head (bulging fontanelle), lethargy, fever or sometimes low body temperature, and difficulty in feeding. However, the appearance of these symptoms varies. For babies who weigh more than 2500 grams, common symptoms are fever, crankiness, seizures, and a swollen soft spot on the head. On the other hand, the most common symptoms in babies who weigh less than 2500 grams are pauses in breathing (apnea), jaundice, and swollen belly (abdominal distention).

A sign called Brudzinski sign can indicate meningitis. This is detected when the baby’s hips bend when their neck is passively flexed.

There are also some early and late signs of meningitis. Check the list below for more information:

Early Signs of Meningitis:

Temperature instability (either fever or low body temperature)
Lethargy
Feeding intolerance

Late Signs of Meningitis:

Seizures
Bulging fontanelle
Neck stiffness (Nuchal rigidity)
Slow heart rate (Bradycardia)
Low blood pressure (Hypotension)

Testing for Neonatal Meningitis

Diagnosing meningitis in newborns can be a complex process due to factors like the baby’s age at birth, when symptoms first show up, where the baby lives, and how subtly symptoms may appear. It can also be difficult because symptoms can vary greatly among different babies. Newborns, because they have immature immune systems, can go from appearing healthy to becoming very sick in a short amount of time and are at high risk for meningitis.

To diagnose meningitis, doctors typically perform a lumbar puncture, which allows them to collect a sample of cerebrospinal fluid (CSF) – a clear, colorless fluid that surrounds the brain and spinal cord – for testing in a lab. It’s currently recommended that all newborns with confirmed or suspected sepsis (a life-threatening condition caused by the body’s response to an infection) should have a lumbar puncture. However, research has shown that not all patients with sepsis undergo this procedure.

According to guidelines from the American Academy of Pediatrics for reviewing feverish babies from 8 to 60 days old, key recommendations include:

– Check CSF for possible infections and bacterial culture in babies 8 to 21 days old with a fever.
– If the baby has more than the normal number of white blood cells in the CSF and there is a high prevalence of enterovirus in the local area, conduct a polymerase chain reaction (PCR) test to check for enterovirus.
– Get PCR testing for herpes simplex virus (HSV) in infants at high risk for HSV. This includes babies born to mothers with genital HSV lesions, mothers who had a fever 48 hours before or 48 hours after delivery, or babies with more than the normal number of white blood cells in the CSF but no positive gram stain result.

In babies aged 22 to 28 days, CSF analysis may be needed if the baby has abnormal inflammation indicators and/or no other identified cause of infection or fever. In this age group, all patients with fever should have their urine tested for infections.

Research also suggests that babies under 60 days old with bacterial meningitis typically have noticeable results on a gram stain (a type of test used to identify bacteria) or an abnormal number of white blood cells in the CSF. These babies should be monitored in a hospital until their test results come back. The amount of time it may take to identify the cause of infection can vary, but most pathogens are usually detectable within 24 hours.

PCR assays that can detect multiple bacteria have a higher detection rate than traditional cultures. PCR testing is also essential for diagnosing HSV involvement in the central nervous system.

Lumbar punctures, however, can be deferred in certain situations. For example, if a baby exhibits no symptoms and is only being considered for a lumbar puncture due to maternal risk factors, then the procedure can be safely delayed unless there are clear signs of infection.

The experts have differing opinions regarding the use of imaging technology in diagnosing meningitis in newborns. Some suggest that a sonogram should be performed for every infant with signs of meningitis, whereas others recommend a sonogram only if there’s suspicion of neurological complications. Regardless, most experts suggest cranial sonography as a first step, followed by a brain MRI. These tests help doctors evaluate neurological tissue and identify organic complications of the infection, like hydrocephalus, a common complication of meningitis that can be detected by neuroimaging.

Treatment Options for Neonatal Meningitis

Doctors recommend different treatments for suspected early-stage meningitis in newborns depending on the region, local bacteria, and specific expertise of the medical professional. The typical starting treatment includes ampicillin and either an aminoglycoside, such as gentamicin, or an expanded spectrum cephalosporin. All the antibiotics are given at doses suitable for newborns’ age and consideration is given to growing concern about bacteria developing resistance to ampicillin.

However, in some developing countries, World Health Organization standards suggest starting treatment with ampicillin or penicillin plus gentamicin, retaining cephalosporins for secondary treatment. It’s worth noting that a large percentage of infections causing meningitis in infants were found to be resistant to ampicillin, but this antibiotic still needs to be included in the initial treatment.

For newborns displaying symptoms of what is known as late-onset meningitis, which typically arises after the first week, additional antibiotics targeting specific types of bacteria found in hospitals may be needed. These are usually given when there is a high suspicion of infection acquired in the hospital. Among them, vancomycin is commonly added to the initial treatment plan. Some experts might also recommend a carbapenem instead of the expanded-spectrum cephalosporin, particularly when the baby has had a long stay in the hospital. However, this isn’t always necessary, as babies who were discharged from the hospital after birth and returned with late-onset meningitis might be treated the same way as those with early-onset meningitis.

If the patient doesn’t show improvement within 24 to 48 hours, the fluid collected from a lumbar puncture (also known as spinal tap) should be tested again. Definitive treatment will begin once the specific cause of the meningitis is identified. The duration of the treatment varies depending on various factors, the type of organism causing the meningitis, the baby’s reaction to the treatment, and any findings from brain scans or other tests.

Usually, a minimum treatment duration is prescribed: 14 days for infections caused by GBS and L. monocytogenes, and 21 days for infections caused by gram-negative organisms. If clear signs of the Herpes Simplex Virus (HSV) are present, doctors will typically begin an investigative evaluation and start treatment for neonatal HSV.

Though there are various options available to target and treat neonatal meningitis, it’s always essential to use caution and approach each case based on individual patient factors and the specifics of the infection.

Diagnosing neonatal meningitis in newborns isn’t always straightforward, as other non-infectious medical conditions can cause similar symptoms such as seizures, irritability, poor feeding, and fever. Once infections arising from bacteria and viruses affecting the brain and spinal cord are eliminated from consideration, there could be other reasons for these symptoms, including:

Neonatal seizure disorders
Genetic disorders that affect the body’s metabolism (Inborn defect of metabolism)
Bleeding within the brain (Intracranial hemorrhage)
Abnormality in a blood vessel in the brain (Cerebral aneurysm)
Clotting in the brain’s veins (Central venous thrombosis)
Bacterial infection spreading through the body, but not affecting the nervous system (Sepsis from non-neurologic foci)

What to expect with Neonatal Meningitis

Despite a drop in death rates, newborn meningitis is still associated with high levels of sickness. In other words, even though fewer newborns are dying from meningitis, many still fall very ill. Every year, globally, around 190,000 cases of death due to this disease are recorded. The death rate varies drastically between different countries. More developed countries such as those in the West see a death rate of about 10% to 15%, majorly seen in prematurely born babies. Whereas in less developed, lower-income countries, the death rate could go up to 58%. Furthermore, amongst the babies who survive, nearly 23% experience moderate to severe developmental issues.

In wealthier countries, 20 to 50% of surviving babies have neurological complications. An in-depth study observed babies surviving meningitis in their first 18 months and found that 32% experienced developmental issues, of which 18% showed moderate to severe impairments. It’s also worth noting that the risk of death remains higher five years after suffering from the disease compared to babies who never had the disease.

According to research carried out in Tunisia, 21.6% of babies had neurological complications. Factors like respiratory distress, low birth weight, shock, and having fewer than 500 cells per cubic millimeter in the blood (pleocytosis) indicated a worse prognosis or outcome. Interestingly, incorporating ‘ofloxacin’ (an antibiotic) into the treatment plan led to fewer neurological complications in surviving babies. Supporting this, another study noted feeding difficulties in babies and concurrent pneumonia as indicators of poor outcomes. Moreover, high protein levels in the fluid surrounding the brain and spinal cord (CSF) during and after the illness led to poorer outcomes.

Most studies conclude that the severity of infection is directly proportional to the outcomes, but there is no difference in outcomes based on the type of pathogen, except in the case of an MDR (multi-drug resistant) organism. A study reported a higher fatality rate (58.8%) in babies with MDR meningitis compared to those with non-MDR meningitis (9.5%).

Clinical symptoms like seizures, irritability, bulging at the soft spot on a newborn’s head, stiffness in the back of the neck, sleepiness or coma, low blood pressure, and low white blood cell count could also predict poor outcomes in surviving babies.

On the brighter side, babies with enteroviral and parechovirus meningitis generally showed favorable outcomes. Even though 35% of these babies had abnormal brain scans (MRIs), all of them displayed normal vision, hearing, and neurological development after a year.

Possible Complications When Diagnosed with Neonatal Meningitis

If someone constantly has bacteria in their blood or cerebrospinal fluid (the fluid in your spinal cord and around your brain), it could be a sign there are complications from meningitis. These complications can include:

A blockage in the brain’s fluid-filled structures (obstructive ventriculitis)
A pus-filled infection beneath the outermost layer of the brain (subdural empyema)
Multiple small blood clots
Collections of pus in the brain (intracranial abscesses)
Or pus-filled infections near the membranes of the brain and spinal cord (parameningeal abscesses)

In a long-term study in the UK, the most common complications from bacterial meningitis were found to be “ventriculitis,” water on the brain (hydrocephalus), and fits or seizures (convulsions), which combined happened in about 26% of cases. Ventriculitis is more common with a type of meningitis caused by gram-negative bacteria and can become chronic, making the brain’s fluid-filled structures have partitions. It is more common in children who have bleeding inside these fluid-filled structures due to being born too early or infections.

Bacteria from the Enterobacteriaceae family are the most common cause of brain abscesses after a cerebrospinal fluid infection. A potential long-term effect of meningitis in newborns is hearing loss. Some experts recommend testing the ability of additional corticosteroids to reduce hearing loss and neurological complications of this disease. A possible complication of bacterial meningitis in newborns is an ischemic stroke, a stroke caused by blocked blood vessels. This, and clotting in the brain’s channels that drain blood (cerebral sinovenous thrombosis), are possible complications of a type of meningitis caused by group B streptococcus bacteria in newborns.

Preventing Neonatal Meningitis

It’s important for everyone to know about the risk of bacteria being passed from mother to baby during pregnancy. This can help lessen the chance of diseases like neonatal meningitis. Because of this, World Meningitis Day takes place on April 24th each year to help raise awareness about this issue.

One way we can prevent neonatal meningitis is through thorough tests and preventative treatment. Specifically, antibiotics given to mothers who carry a certain bacteria (GBS) during labor have helped to lower the number of early cases of GBS infections. However, these measures don’t seem to affect cases that occur later on.

Right now, vaccines are being created that could help to prevent neonatal meningitis. There are even trials underway for vaccines aimed at preventing GBS and E-coli, which, if given to mothers, could potentially reduce neonatal meningitis cases by two-thirds.

Frequently asked questions

The prognosis for neonatal meningitis can vary depending on several factors, including the severity of the infection and the type of pathogen involved. However, some general trends can be observed: - In wealthier countries, 20 to 50% of surviving babies have neurological complications. - Amongst the babies who survive, nearly 23% experience moderate to severe developmental issues. - The risk of death remains higher five years after suffering from the disease compared to babies who never had the disease. - Factors like respiratory distress, low birth weight, shock, and pleocytosis (low white blood cell count) indicate a worse prognosis. - Incorporating the antibiotic 'ofloxacin' into the treatment plan can lead to fewer neurological complications in surviving babies. - High protein levels in the cerebrospinal fluid (CSF) during and after the illness can lead to poorer outcomes. - The type of pathogen does not significantly impact outcomes, except in the case of multi-drug resistant (MDR) organisms, which have a higher fatality rate.

Neonatal meningitis can be caused by various pathogens, including bacteria and viruses. The specific causes can depend on factors such as the baby's gestational age, birth weight, whether the infection was acquired in the hospital or community, and the presence of certain bacteria such as Group B Streptococcus or E. coli. Other pathogens that can cause neonatal meningitis include Listeria monocytogenes, Enterococcus sp, Streptococcus pneumoniae, Candida sp, Cronobacter sakazakii, and Citrobacter sp. Babies exposed to HIV or those with indwelling medical devices are also at a higher risk.

The signs and symptoms of Neonatal Meningitis can vary depending on the weight and age of the newborn. Some common signs and symptoms include: - Seizures - Swollen soft spot on the head (bulging fontanelle) - Lethargy - Fever or sometimes low body temperature - Difficulty in feeding For babies who weigh more than 2500 grams, common symptoms are: - Fever - Crankiness - Seizures - Swollen soft spot on the head For babies who weigh less than 2500 grams, common symptoms are: - Pauses in breathing (apnea) - Jaundice - Swollen belly (abdominal distention) There is also a sign called Brudzinski sign that can indicate meningitis. This is detected when the baby's hips bend when their neck is passively flexed. In addition, there are early and late signs of meningitis. The early signs include temperature instability (either fever or low body temperature), lethargy, and feeding intolerance. The late signs include seizures, bulging fontanelle, neck stiffness (Nuchal rigidity), slow heart rate (Bradycardia), and low blood pressure (Hypotension).

The types of tests needed for neonatal meningitis include: - Lumbar puncture to collect a sample of cerebrospinal fluid (CSF) for testing in a lab - Polymerase chain reaction (PCR) test to check for enterovirus if the baby has more than the normal number of white blood cells in the CSF and there is a high prevalence of enterovirus in the local area - PCR testing for herpes simplex virus (HSV) in infants at high risk for HSV, such as babies born to mothers with genital HSV lesions or mothers who had a fever before or after delivery - Gram stain to identify bacteria or an abnormal number of white blood cells in the CSF for babies under 60 days old with bacterial meningitis - Urine test for infections in babies aged 22 to 28 days with abnormal inflammation indicators and no other identified cause of infection or fever - Imaging tests such as cranial sonography and brain MRI to evaluate neurological tissue and identify complications like hydrocephalus - Additional tests may be needed to identify the specific cause of the meningitis and guide treatment.

Neonatal seizure disorders, Genetic disorders that affect the body's metabolism (Inborn defects of metabolism), Bleeding within the brain (Intracranial hemorrhage), Abnormality in a blood vessel in the brain (Cerebral aneurysm), Clotting in the brain's veins (Central venous thrombosis), Bacterial infection spreading through the body, but not affecting the nervous system (Sepsis from non-neurologic foci)

The side effects when treating Neonatal Meningitis can include complications such as obstructive ventriculitis (a blockage in the brain's fluid-filled structures), subdural empyema (a pus-filled infection beneath the outermost layer of the brain), multiple small blood clots, intracranial abscesses (collections of pus in the brain), and parameningeal abscesses (pus-filled infections near the membranes of the brain and spinal cord). In a long-term study in the UK, the most common complications from bacterial meningitis were ventriculitis, hydrocephalus (water on the brain), and convulsions (fits or seizures), which occurred in about 26% of cases. Other potential complications include brain abscesses, hearing loss, ischemic stroke (a stroke caused by blocked blood vessels), and cerebral sinovenous thrombosis (clotting in the brain's channels that drain blood). Some experts recommend testing the use of additional corticosteroids to reduce hearing loss and neurological complications.

You should see a pediatrician or a neonatologist for neonatal meningitis.

In the United Kingdom, the incidence of bacterial meningitis is 0.38 per 1000 live births, and the incidence of viral meningitis is 0.83 per 1000 live births. In Canada, there are 2.2 to 3.5 cases of meningitis for every 1000 neonatal intensive care admissions over seven years. In developing countries, meningitis affects between 0.8 and 6.1 per 1000 live births, with a mortality rate as high as 58%.

Neonatal meningitis is treated with a combination of antibiotics, such as ampicillin and either an aminoglycoside or an expanded spectrum cephalosporin. The specific treatment may vary depending on the region, local bacteria, and the expertise of the medical professional. In some developing countries, the World Health Organization suggests starting treatment with ampicillin or penicillin plus gentamicin. Additional antibiotics targeting specific types of bacteria found in hospitals may be needed for late-onset meningitis. The duration of treatment varies depending on factors such as the type of organism causing the meningitis and the baby's response to treatment.

Neonatal meningitis is a condition characterized by inflammation of the membranes surrounding the brain and spinal cord in newborns. It can have severe long-term consequences and is caused by various germs, including bacteria, fungi, and viruses. Diagnosis can be challenging due to the variability of the causative germs and the subtle symptoms in babies. Performing a lumbar puncture is recommended to rule out neonatal meningitis in babies with confirmed or suspected sepsis.