Dr. Allen Cherer is an accomplished neonatal care specialist with decades of medical experience.

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Some Common Health Problems in Newborns

Most babies are vulnerable to health problems after they’re born. They may be born with a variety of conditions, and they can contract others easily. If you’re a new parent, it’s important that you know about the signs and symptoms of these conditions so that you can take the necessary steps to prevent or treat them. Here are some of the most common health problems seen in newborns today.

Jaundice

Jaundice is a common health issue that affects infants and children. It occurs when a baby has an excessive amount of bilirubin in their blood. This condition usually occurs because their liver is not mature enough to remove the excess bilirubin.

Although it usually disappears within 2 to 3 weeks of being born, it can still be a symptom of an underlying issue. Parents should consult their doctor if their baby’s jaundice persists longer than 3 weeks.

Respiratory Distress

This condition can occur when the baby’s nasal passage gets blocked, causing insufficient oxygen to enter the body. It can take a couple of hours for the baby to start breathing normally, and it can continue until the bluish coloration disappears. If the condition persists, it’s important that the child gets checked by a healthcare professional.

Abdominal Distension

Healthy infants and newborns are prone to experiencing abdominal distension. One of the most common causes of this condition is the baby’s swallowing of excess air. If the belly feels swollen or hard, this could be caused by constipation or gas.

As the baby’s body begins to adjust to eating, this condition should eventually resolve itself. However, if it persists, it can lead to a serious issue with the internal organs.

Colic

Although colic is very common in babies, it can be hard for parents to handle due to its nature. Although the exact causes aren’t known, it’s believed that it can be caused by various factors such as gas, hormones, overstimulation by light or sound, or even a growing digestive system.

Early signs of colic usually start to appear in 2 to 3 weeks and typically only last about 3 months. However, if it persists, it can be caused by an underlying health issue. It’s important to consult a doctor to diagnose the condition.

A Brief History Of Today’s Neonatal Intensive Care Unit

When a baby is born prematurely or has a critical illness, the neonatal intensive care unit is usually the place to go. It has the latest equipment and medical experts to give that child the best chance of survival. This hasn’t always been the case though.

 

Before the 1950s, most premature and low-risk newborns were sent home. They didn’t receive the specialized care they needed, and many of them would not live past their first birthday. the NICU has come a long way since those days, so let’s talk about its evolutions through the years.

 

In The Beginning…

Early in the 17th century, scientists and doctors began discussing the care of at-risk and premature infants. During the 19th century, various forms of special care were being developed for these infants. After World War II, hospitals started to create specialized units for these children, becoming what we know today as the NICU.

 

While many medical experts through time were involved in advancing neonatal care, three, in particular, are considered pioneers in the field:

 

French obstetrician Dr. Etienne Tarnier (1828-1897) is known for his work on the well-being of premature infants. He came up with the idea of using a heated isolette to help premature babies stay warm and grow. He was inspired by the French farmers who used similar equipment to hatch chicken eggs.

 

Dr. Pierre-Courcy Budin (1846-1907) was another French obstetrician that devoted his career to improving the care of at-risk infants. He helped educate mothers about proper hygiene and nutrition. He also advocated for the use of gavage, which is a feeding tube that can be inserted into the stomach.

 

Although it’s not exactly clear if he had any medical training, Martin Arthur Couney (1869-1950) became known as the incubator doctor after he studied under Dr. Budin in Paris. He learned about the importance of using incubators for premature infants.

 

He became known for displaying live infants inside incubators at various events, such as fairs and expositions. Through his work, he was able to raise awareness about the importance of using incubators for premature infants.

 

The Rise of the NICU

The increasing number of studies that discovered the importance of humidity and heat in the survival rates of at-risk infants prompted more hospitals to create special care units for premature newborns. One of the first innovations to be used was the Hess incubator, which was invented by Dr. Julius Hess at Chicago’s Reese Hospital.

 

Louis Gluck, a doctor from the US, was another pioneer in the field of neonatal medicine. His research highlighted the risks of infection in premature babies.

He learned that poor hand hygiene could lead to infections among the babies in the special care unit. He then came up with a series of protocols that were designed to improve the hygiene of premature infants, as well as how we approached the design of these special care units. This led to what we know as the first American NICU unit opening at Yale New Haven Hospital in October 1960.

 

Getting To Today

Jacqueline Kennedy, wife of President John F. Kennedy, gave birth to a boy in August 1963. Unfortunately, he only lived for a couple of days before dying due to respiratory distress syndrome. This incident became very significant due to the seriousness of the situation and how public it was made, prompting professionals all over the world to take a closer look at how we approach the health challenges of premature infants.

 

Advancements in medical technology during the 1960s into the 1990s allowed any baby born alive to have a better chance of survival. As a result, multiple births became more common. This also led to more coverage of the care provided to premature babies.

 

During the 1990s, the number of hospitals that provide intensive care for premature infants grew. These facilities were equipped with highly trained medical teams that were able to respond to the needs of these kids.

 

Today, the care and treatment of premature and at-risk infants continues to improve due to the advancements in technology and the dedicated staff members of the hospitals that provide these services. It is truly amazing to see how far medical science has come in the field of neonatal medicine.

What does Neonatal Care Entail?

Neonatal care is essential in helping many newborn babies thrive. When a child is born prematurely, has a low birth weight, or has health concerns after birth, they will be cared for in the neonatal care unit. This special care provides personalized treatments based on the individual needs of each newborn. There are different levels of neonatal care. The level of care provided depends on the baby’s needs and many infants may go through several different levels as their condition changes. 

 

Parents may feel anxious or fearful when hearing that their child will be taken to the neonatal care unit. This is understandable, but the medical care teams are experienced in helping parents understand procedures and providing information each step of the way. When a baby first arrives in the neonatal care unit, it will be assessed thoroughly so the medical team can come up with the best medical care strategy. The unit may be filled with many machines and devices that can look scary to a new parent. That’s why the staff takes great care in comforting parents and ensuring that they stay informed about their child’s health. 

 

Neonatal care may involve regular testing and scanning to keep track of blood sugar, platelets, and white blood cells. The neonatal care unit is also capable of performing x-rays, MRIs, and other essential scanning procedures. These tests allow the medical care team to better understand the needs of the baby so they can tailor treatments based on those needs.

 

The medical staff working in the neonatal care unit understand that parents may be quite scared about their child needing extra care after birth. They do everything possible to allow parents to hold and interact with their children. Parents are encouraged to ask questions, which can help them better understand the need for various procedures. In many cases, a parent can be present to comfort their child through holding or touch. 

 

The neonatal care unit provides specialized care for newborns that need additional attention after birth. Parents may be present during many procedures and are encouraged to actively participate in comforting their new baby when possible. While it may seem like a scary place at first, the neonatal care unit is designed to help babies heal and thrive.

What is Neonatal Abstinence Syndrome?

Neonatal abstinence syndrome (NAS) is a condition that occurs in newborns who were exposed to addictive substances in utero. When a pregnant mother uses drugs or alcohol, the baby can be born with NAS. This condition can cause various health problems for the infant, including seizures, feeding problems, and respiratory distress. In this article, we will discuss NAS’s causes, symptoms, and impact.

 

 Causes of Neonatal Abstinence Syndrome

 

Several substances can cause NAS in a newborn, including opioids, and marijuana. When an expectant mother uses any of these drugs, the baby is at risk for developing NAS. The use of prescription painkillers is a major contributor to the development of NAS. 

 

Symptoms of Neonatal Abstinence Syndrome

 

The symptoms of NAS vary depending on the mother’s drug during pregnancy. However, common symptoms include seizures, feeding problems, respiratory distress, and irritability. These symptoms can vary from mild to severe, and they usually develop within the first few days after birth. In some cases, NAS can lead to death.

 

Impact of Neonatal Abstinence Syndrome on the baby

 

The impact of NAS on the baby can be devastating. The symptoms can cause physical and developmental problems, and they can also lead to long-term health issues. Some of the complications that babies with NAS may experience include:

 

  • Respiratory problems
  • Feeding difficulties
  • Seizures
  • Developmental delays
  • Behavioral problems
  • Low birthweight
  • Jaundice.

 

How Neonatal Abstinence Syndrome is treated

There is no one-size-fits-all treatment for NAS. Treatment depends on the severity of the baby’s symptoms and the mother’s drug. Some common treatments include:

 

  • Medication: Medications are often used to help relieve NAS symptoms. The most common medication used to treat NAS is methadone, which is an opioid agonist.
  • Nutritional support: Babies with NAS often have trouble feeding, so they may need to be fed through a tube.

 

Prevention of Neonatal Abstinence Syndrome

 

The best way to prevent NAS is to avoid using drugs and alcohol while pregnant. If you are pregnant and you need help to stop using drugs or alcohol, there are several resources available to you, including counseling and addiction treatment programs. It is also important to get regular prenatal care so that your doctor can monitor your baby’s development. If you think you may have an issue with drugs or alcohol, talk to your doctor about it. Getting help early on can make a big difference in the health of you and your baby.

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Neonatal Intensive Care Trends in 2021

Neonatal intensive care (NIC) is a term used to describe the care of premature, or very premature infants in an intensive setting. NIC is often necessary to save the infant’s life and provide long-term care for them. In 2021, there will be an increase in the number of babies born with significant medical conditions, such as heart disease and leukemia. To provide the best possible care for these infants, it is essential to understand the trends in NIC.

NICU admission and race/ethnicity

In the United States, several NICU admissions are racially, and ethnically diverse. In 2011, the NICU admissions of white babies were more than double that of black, and Hispanic infants. The NICU admission rates for black babies are still much less than that of white babies, but it is increasing faster. In 2011, the rate for Hispanic babies was three times the rate for white babies. This trend will continue to grow over time as more Hispanics become pregnant, and give birth in the United States.

Medication use

During the last few years, there has been a decrease in the number of premature infants’ medications. This trend is partly because there has been a decrease in the number of medications prescribed to infants during this period. The use of various pharmaceuticals has also decreased over time. The decrease in medication use is positive because it can help with other aspects of NIC care, and reduce potential side effects from medication use.

Newborn screening

The rate at which infants are screened for certain diseases increases over time. In 2011, newborn screening for Down syndrome was more than double that of 2001. This increase is likely because more people are becoming aware of Down syndrome, and are seeking out prenatal care. There is also an increased awareness of preconception screening for Down syndrome risks.

Conclusion

The above points are just a few of the many trends in NIC over the next few years. It is essential to understand these trends because they can help to shape the future of NIC. To provide the best care for all infants, it is essential to understand these trends and work together with other professionals to provide a high-quality NIC.

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Understanding Vaccine Mandates

Vaccines have saved millions of lives over the years by preventing diseases like polio, measles, and diphtheria from spreading. But as more people refuse to vaccinate their children because of unfounded fears, those numbers could rise again. This post will explore the mandates of a vaccine.

Prevents diseases

Vaccines are typically thought to work by stimulating the body’s immune system to defend against disease-causing microorganisms, called pathogens. The weakened or killed virus in a vaccine cannot make you sick, but your body can develop the ability to fight the real thing. This is called immunity and the only way to build it is through vaccines.

Safe to use

Vaccines are tested extensively for safety and effectiveness before they come to market. In the United States, vaccines must be approved by the Food and Drug Administration (FDA). This means that vaccines have met strict scientific guidelines, proving them safe and effective. Most vaccine reactions are mild such as fever, redness or soreness where they were given, or temporary aches. Severe side effects are very rare but may include allergic reactions, a severe allergic reaction called anaphylaxis can occur within minutes after vaccination occurs in someone who is known to be allergic to certain vaccine components.

Prevent epidemics

If a critical number of people in a community are vaccinated against the same disease, the odds of outbreaks become very small. This is called ‘herd immunity. Even those who cannot be vaccinated because they have compromised immune systems or other conditions benefit from herd immunity. This is why it is so important for everyone to get vaccinated, especially when an epidemic is looming.

Protects future generations

When enough people are vaccinated, diseases stop spreading. This protects everyone, including future generations because many vaccine-preventable diseases have no cure. Preventing disease through vaccination is one of the most successful and cost-effective health strategies in history. It is crucial to maintain high vaccination rates to ensure that these diseases do not return. Vaccines were responsible for making our world what it is today with all the achievements we’ve had so far.

Vaccines have saved millions of lives over the years by preventing diseases like polio, measles, and diphtheria from spreading. We must keep vaccinating ourselves and our children to protect against outbreaks.

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Avoiding the Delta Variant While Outdoors

For the majority of the pandemic, it has been recommended that people gather outdoors if they must gather at all, but that appears to be changing a little. The Delta variant of covid-19 has changed the playing field even among the vaccinated. Initially, we were advised to take as much of our daily lives outdoors as possible in order to reduce transmission of the virus. Makes sense, right? Well, with how the Delta variant has changed things, we thought we should put together a list of measures people can take to reduce their risk of exposure to the Delta Variant.

Mask Up!

First and foremost, the easiest thing a person can do to reduce transmission, regardless of whether or not they’re indoors, is to wear a mask. Surgical masks, respirators, and N95 masks have all been shown to reduce transmission by limiting the number of aerosolized particles that spread in our breath, sneezes, and coughs.

Get Vaccinated

Vaccinated people are 25 times less likely to fall significantly ill with the delta variant. Getting vaccinated is simple, free, and absolutely encouraged right now. It is the best way we can help reduce transmission and do our part to flatten the curve. By bolstering our immune systems through vaccination, we can ensure that our bodies will be better equipped to fight off the virus more effectively, and thereby lowering our risk of infecting someone else.

Social Distancing

Beth K. Thielen, MD, Ph.D., is an assistant professor of pediatrics at the University of Montana has encouraged people to continue socially distancing even when outdoors. The Delta Variant has been shown to spread even when outdoors, which has some medical professionals, like Dr. Thielen, rightfully suggesting that we revert to older, more established, and cautious preventative measures.

Conclusion

The increase in both breakthrough cases and outdoor infections indicates that we might need to exercise a little more caution with the new prominence of the Delta Variant. Doing our part to minimize transmission of the virus has become our civic duty as citizens not of our countries, but of humanity itself. The tips and recommendations here aren’t comprehensive by any means, but all of them offer a good rule of thumb to go by.

Tackling Postpartum Issues

Tackling Postpartum Issues by Dr. Allen ChererWorking in the field of neonatal care, I know all too well the health risks that come with pregnancy and childbirth, especially among women who can’t readily access health care.  Some common (and serious) postpartum health conditions include diabetes, hypertension, and depression, all of which are more common among racial and ethnic minority women.  However, it’s hardly a lost cause, and doctors can do their part to connect women suffering in the pregnancy and postpartum period to healthcare.  I recently read an article by Elizabeth A. Howell, whose work creating an “intervention design” at Mount Sinai is based around providing postpartum care to women.  This was recently published in the Maternal and Child Health Journal.  

According to the Healthcare Effectiveness Data and Information Set (HEDIS), at least 80 percent of commercially-insured women in this country have a timely postpartum visit.  Yet among those insured by Medicaid, that percentage goes down to about 60.  This is due to various factors: transportation, child-care demands, money, and poor doctor-patient communication.  While there isn’t an “easy fix” to this problem, reducing the barriers between patient and doctor makes it much easier for women to receive the necessary postpartum care.  In the article, Howell outlines various ways that her design reduces that barrier: education about the risks and importance of postpartum care, community resources, and financial incentives for providers who help make sure women return for postpartum care.  Since such a large percentage of patients are Spanish-speakers, her interventions are available in both English and Spanish.  

So far, Howell’s program seems to be yielding some good results: the visit rate for Healthfirst patients at her hospital was up to 71 percent through 2016.  Patients, many of whom are socially isolated, have also expressed their appreciation.  Through my experience, I can tell you just how serious the postpartum period is for the health of mothers as well as children.  I’ve thought about the many positive benefits of assuring comprehensive postnatal care.  In the end, I think this may turn out to be the best way to improve prenatal care, and consequently newborn outcomes.

Tackling Rotavirus

National Infant Immunization Week Blog-a-thon with woman holding baby. #ivax2protect

Rotavirus gastroenteritis is the leading cause of diarrhea-associated hospitalizations and death in children younger than 5 years of age. Rotavirus illness is caused by a virus which enters the body by mouth and infects the intestines. It is a particularly hardy and contagious virus, capable of surviving on inanimate surfaces for long periods and spreading readily from child to child and also to adults. Large quantities of virus are shed in the stool both prior and following acute illness which is characterized by fever, vomiting, and watery diarrhea. Illness typically lasts 3-7 days; death may ensue due to severe dehydration. Since the infection is caused by a virus, antibiotics and antiparasitic drugs are ineffective, and care is primarily supportive. Prior to the development of effective vaccines, 80% of children in the U.S. would develop rotavirus gastroenteritis. Elsewhere in developing countries, the numbers were staggering with more than 500,000 deaths occurring annually in children under 5 years old.

The first rotavirus vaccine, RotaShield (Wyeth Laboratories) was licensed in the United States in 1998 but was withdrawn in 1999 due to a suspected association with intussusception, a type of bowel obstruction. In 2006, RotaTeq (GlaxoSmithKline) was FDA approved, followed by Rotarix (Merck) in 2008. Both are live, attenuated, oral vaccines requiring either a 3 dose or a 2 dose series and have shown significant efficacy in the range of 80-90% in middle and high income countries. Prior to 2006 when routine rotavirus vaccination was recommended, rotavirus gastroenteritis was estimated to result in 400,000 visits to physician’s offices, 200,000 visits to Emergency Rooms, 55,000 hospitalizations, and 20-60 deaths annually among children under 5 years of age in the U.S. for an estimated total cost close to $300 million. Since introduction of the vaccine, the impact has been striking; hospitalizations and rotavirus-related Emergency Room visits have decreased by 80%. In addition, by vaccinating infants, serious rotavirus infections among older children and adults have demonstrated similar declines, presumably through the so-called “herd effect” resulting from wide-spread immunization practice. In summary, clinical trials and experience of rotavirus vaccines in middle and high income countries have demonstrated high efficacy against serious rotavirus disease. Rotavirus vaccination works!

Despite the high efficacy rates of RotaTeq and Rotarix vaccines in middle and high income countries, clinical studies consistently demonstrate lower efficacy rates in the range of 37-61% with either vaccine in the lowest income nations where the burden of rotavirus infection is greatest. Such performance is typical of other live oral vaccines in similar populations. The reasons are not completely understood, but factors such as earlier onset of recurrent episodes of infectious diarrhea, different gut microbiome, the presence of neutralizing antibodies, poor nutritional status, and varying circulating rotavirus strains may play a role. Nevertheless, even a moderately effective vaccine can have a huge public health impact when introduced into a population where the burden of disease is great, especially when combined with the herd protection that occurs when most children in an area are vaccinated and immune.

In 2000, the Global Alliance for Vaccines and Immunization (Gavi) was founded as a public-private global health partnership with the intent to improve childhood immunization coverage in poor countries and increase access to new vaccines. By design, Gavi leverages not only financial resources but also expertise to make vaccines more available, affordable, and their provision more sustainable. The two current rotavirus vaccines obtained prequalification by the World Health Organization (WHO) in 2008 which followed with UNICEF procurement of the vaccines through the financial support of Gavi. These vaccines have been introduced in 42 Gavi-eligible countries and in 6 additional countries classified as low and middle income and have had a major impact on rotavirus-associated hospitalizations and deaths in all settings.

According to WHO estimates in 2013, approximately 215,000 children under 5 years of age die each year from vaccine-preventable rotavirus infections with almost half of them in 4 countries: India, Pakistan, Nigeria, and Democratic Republic of Congo. Ten countries account for almost 2/3 of all deaths. It is in this context that findings recently published in the New England Journal of Medicine related to a new vaccine against rotavirus are incredibly encouraging. The study reported by Isanaka et al. was conducted in Niger in Sub-Saharan Africa, a region with the highest rate of death associated with rotavirus disease and where the current cost of vaccines is probably unsustainable and where refrigeration and transportation are unreliable. The new vaccine, BRV-PV (Rotasil), is a live, oral rotavirus vaccine manufactured by Serum Institute of India and is lower in cost relative to existing vaccines and heat stable for as long as 6 months at 104 degrees F. and for 2 years at 98.6 degrees F. In a double-blind, placebo-controlled randomized trial including over 4000 healthy infants, the new vaccine was found to have a calculated efficacy rate of 67% with no apparent short term adverse events. Since existing vaccines are costly and require refrigeration, the new vaccine provides major advantages in resource-constrained countries where the burden of rotavirus is greatest. If further surveillance continues to yield good findings, the new vaccine promises to provide a giant step in the progress against rotavirus.

 

Congenital Cytomegalovirus Infection and Hearing Loss

ongenital Cytomegalovirus Infection and Hearing Loss

It has been over 50 years that the association between congenital Cytomegalovirus (CMV)  infection and hearing loss was described by Medearis et al. During that time, advances in understanding the pathogenesis and the natural history of the disease have been made. It is now acknowledged that CMV infection is not only the most common congenital viral infection in the world but also the leading non-genetic cause of childhood sensorineural hearing loss. The world-wide incidence of congenital CMV infection is estimated to range from 0.06% – 2.4% of all live births. As many as 10-15% of infected neonates are symptomatic at birth, presenting with a variety of signs/symptoms including growth failure, anemia, extramedullary hematopoiesis, thrombocytopenia, hepatosplenomegaly, intracranial calcifications, microcephaly, and chorioretinitis. Mortality is <5%, but as many as 50% of survivors will demonstrate  long-term sequelae, primarily sensorineural hearing loss and neurodevelopmental delay. On the other hand, the great majority of congenitally infected neonates are asymptomatic and may be totally unrecognized. They generally have a much better prognosis. Notably, however, approximately 10% of these asymptomatic infants will also manifest sensorineural hearing loss, often late in onset and progressive in nature, and some element of neurodevelopmental delay. Hence the global burden of congenital Cytomegalovirus infection is significant.

Cytomegalovirus is ubiquitous in humans and infects 50-85% of adults in the United States by 40 years of age. Virus excretion rates from urine and saliva in children from 1-3 years of age in child care centers are reported to range from 30-40% but can be as high as 70%. Generally, acquired infection  in adults and children is mild and inconsequential in terms of long-term sequelae. CMV, like Herpes Simplex and Varicella Zoster, belongs to the herpesvirus family. All three may cause congenital and perinatal infections. Transmission of the virus can occur vertically to the fetus during pregnancy with the highest risk of infection occurring during the first half of gestation. Maternal infection can occur following initial exposure, with reactivation of the virus following previous infection, or with reinfection with a different strain of the virus. Symptomatic infection occurs with similar frequency in newborns born to women with initial CMV infection (primary infection) and those born to women who were seropositive before pregnancy (non-primary infection). Then too, the severity of newborn disease and the rates of CMV-associated sensorineural hearing loss do not differ between primary and non-primary infection. Studies since 2003 have reported treatment benefit in terms of hearing  and neurodevelopmental outcome of intravenous ganciclovir for 6 weeks and subsequently in 2013 with its oral prodrug valganciclovir for 6 months. The American Academy of Pediatrics Red Book, 2015 edition, recommends antiviral treatment for those newborns with symptomatic congenital CMV infection with or without CNS involvement provided it can be initiated within the first month of life. The quandary, of course, arises when the definition of “symptomatic” is not clear. Suggestions have been offered, but none has been universally accepted. In addition, the Red Book specifically advises against antiviral treatment for those asymptomatic patients with congenital CMV infection, although a number of them are at risk for long-term sequelae.

In 2000, the Joint Committee on Infant Hearing endorsed Universal Newborn Hearing Screening (UNHS). Prior to that time, only at risk newborns for hearing impairment were screened, and it was estimated that close to 50% of all children with hearing loss were undiagnosed until 18 months to 3 years of age. It is generally accepted that in order to achieve linguistic and communicative competence, diagnosis and intervention must take place before 6 months of age. The aim of UNHS is to screen all newborns before 1 month of age and have confirmation of hearing loss in infants who do not pass through a complete audiologic evaluation by 3 months of age. A limitation of UNHS is not all cases of childhood hearing loss, especially those with late onset and/or progressive loss, will be detected. Clearly, newborns with congenital CMV infection, specifically those who are asymptomatic and have not been identified, may be missed altogether.

Based on the global nature and incidence of congenital CMV infection, the frequency of late onset hearing loss, and the benefits of early intervention, newborn screening for congenital  CMV infection has been explored  but has not yet been adopted. Dried blood spot  (DBS) PCR for CMV was initially encouraging but recent studies suggest poor sensitivity, and blood viral load does not appear to be sensitive or specific in predicting which infants will develop late onset hearing loss. Newborn saliva and urine PCR for CMV are best to identify congenital CMV infection, but  to date no specific biomarkers have been found to reliably predict which infants will develop late onset hearing loss. Ideally, maternal infection with CMV would be eliminated. An alternative would be to prevent transmission to the fetus or newborn. In the meantime, research continues to better identify and treat  those newborns with congenital infection and prevent the serious sequelae.

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