Hernias and Hydroceles

There are three points to remember if your child has been diagnosed with an inguinal hernia or a hydrocele: 

• An inguinal hernia (or hydrocele) is a different problem in a child than it is in an adult.
• Inguinal hernias and hydroceles are not caused by exercise, crying, or any other physical activity.
• Inguinal hernias and hydroceles are not hereditary; they are basically developmental glitches.

Inguinal hernias form as a direct consequence of normal events in fetal development. At about 12 to 14 weeks of gestation, the gonads (testicles or ovaries) are formed near the kidneys. They gradually descend through the abdomen as the baby develops. If the baby is a boy, the testicles pass through an opening low in the abdomen and into the scrotum; if the baby is a girl, the gonads stop near this opening, and develop into ovaries.

 In about 5 % of children in the United States, this opening does not close properly. This happens more commonly in boys than in girls, and even more often in premature babies. (As a result, about 8 boys will develop inguinal hernias for every girl who does so, and 10-30% of premature infants will be found to have hernias.) The failure of this opening to close potentially allows the contents of the abdomen to travel down into the scrotum (in a boy) or the labia (in a girl). The contents of the abdomen include the intestines, the ovaries, and the clear fluid in which the intestines normally float. If the scrotum or labia are found to contain intestines or an ovary, this is termed an inguinal hernia. If they contain only fluid, this is a hydrocele. The difference between the two is usually just the size of the opening; the basic anatomy is the same in both cases.

Signs and symptoms

There are two periods of time when this condition is typically discovered: during the first year of life, and at 3 to 4 years of age, after the child has been upright and walking. It is unusual to find childhood inguinal hernias after the age of 10.

The primary sign to look for in children is a bulge in the groin extending toward the scrotum or labia. Your child may also complain of pain in that area. If there is firmness or tenderness in the bulge, it may be a sign that an abdominal organ has become trapped (or incarcerated); in this case, the child needs immediate medical attention. When abdominal organs get trapped in hernias, the blood supply to that organ may become choked off. This can result in the loss of an ovary or intestine.

Surgery is the only treatment option for hernias; they do not resolve on their own. 

Epigastric hernias

Epigastric hernias are also congenital conditions (the children are born with them).  These hernias occur as tiny defects in the upper anterior abdominal wall (in the midline, between the umbilicus and the sternum, or breastbone).  Often they are noticed because a little piece of intra-abdominal fat becomes trapped, or incarcerated, in the hernia.  This incarcerated tissue is palpable as a tiny knot just beneath the skin.  While epigastric hernias may be asymptomatic, they are often quite tender, and the child may complain of pain at the site.

Surgery is usually recommended when they are diagnosed, as they will not resolve on their own and may cause more problems as time progresses.

Umbilical hernias

Umbilical hernias form at the site where the umbilical cord passed through the abdominal wall of the developing baby.  Usually, the abdominal wall seals off this "passageway" after birth.  However, in some children this does not occur, and the opening in the abdominal wall persists as an umbilical hernia.

Umbilical hernias are more common in girls than in boys, and are often seen in infants.  They are usually obvious, noticed as protrusions at the umbilicus, which may bulge as the child strains or cries.  More rarely, the defect will be tiny and less visible; the child may be brought to the attention of a doctor because a little piece of trapped intra-abdominal tissue in the hernia is causing pain at the site.

Many of these hernias (unlike inguinal or epigastric hernias!) will close off as the child grows, so immediate surgery is not often recommended for infants with this condition.  However, if the initial hernia is unusually large, is causing the child discomfort, or if the child has reached the age of four or five years without closure, generally, surgery will be recommended. 

Can my child's hernia come back after surgery?

It is rare for any childhood hernias to recur. You do not need to restrict your child's activities or prevent him/her from participating in sports.  Children who are at higher risk for recurrence of inguinal hernias include those who need emergency hernia surgery, premature infants, and children who have increased pressure in the abdomen (such as children with ventriculo-peritoneal shunts or peritoneal dialysis).

Short Bowel Syndrome and Treatment

There are numerous definitions for short-bowel syndrome (SBS). The simplest definition is that there is inadequate intestine to maintain normal nutrition by eating. Because infants and children require increased calories to grow and develop, SBS can have a more devastating effect in these patients.

Before the availability of total parenteral nutrition (TPN, food delivered into the veins), most infants and children with SBS died from malnutrition. The true incidence of SBS is unknown. A Canadian study suggested that it is present in 4.8 per 1 million people. SBS typically is the result of a catastrophic event involving the small intestine and possibly the colon (large intestine). NEC and midgut volvulus from malrotation are the two most common causes of SBS. Other causes are listed in Table 1.

Table 1: Course of Short-Bowel Syndrome in Infants and Children

Necrotizing enterocolitis Midgut volvulus from malrotation Multiple intestinal atresias Gastroschisis Trauma Inflammatory bowel disease

Normal Physiology
The small intestine is completely formed by 20 weeks’ gestation. Most of its growth prior to birth occurs in the third trimester. Before 27 weeks’ gestation, the average length of the small intestine is 115 cm. This length increases to approximately 250 cm with a diameter of 1.5 cm after 35 weeks’ gestation. In contrast, the adult intestine is 600 to 800 cm in length and 4 cm in diameter. The mucosal surface area increases with age. Infants have 950 cm2; adults have 7500 cm2.

The intestine has an enormous capacity to absorb secretions and ingested fluids (Figure 1). There is extra intestine normally which is why a major loss of the intestine may not result in SBS. Absorption occurs through the lining (mucosa) of the small intestine. Nutrients, vitamin B12, calcium, iron, and bile acids are absorbed through the cells of this lining. Mucus covers the surface of the mucosa cells and acts as a trap to hold nutrients in contact with the cell surface. Mucus also acts as a bacterial barrier.

Figure 1. Intestinal function by site. After removal of the intestine, other sites may adapt to assume those functions, as there is overlap of some absorptive function between sites.

Pathophysiology
In patients with SBS, intestinal function depends on multiple factors (Table 2).

Table 2: Factors Influencing Intestinal Function in Short-Bowel Syndrome

Total remaining small intestinal length Etiology of intestinal loss Intestinal loss before versus after birth Remaining intestine (jejunum or ileum) Presence of the ileocecal valve (valve between the large and small intestine) Length of time from removal of the intestine

 

The most crucial factor is the length of the remaining intestine. Removal of the stomach, jejunum, or colon is better tolerated than removal of the ileum (last part of the small intestine). The stomach digests nutrients by the action of acid and enzymes and produces “intrinsic factor,” which is essential for vitamin B12 absorption. The stomach reacts to massive loss of intestine by secreting large volumes of high acid–containing stomach juices at least for a time.

The jejunum (first part of the small intestine) is the site of absorption of most nutrients and minerals, such as calcium, magnesium, and iron. With removal of the jejunum, there is loss of some of the enzymes that break down sugars, which decreases sugar absorption. Unfortunately, bacteria can use these unabsorbed sugars and produce lactic acid. The absorption of the increased lactic acid can lead to increased acid in the bloodstream.

Fat and protein digestion may be reduced if the jejunum is gone. Calcium and magnesium losses are increased. If there is adequate ileum (last part of the small intestine) remaining after loss of the jejunum, however, the loss of the jejunum is better tolerated.

Carbohydrate, protein, fluid, and electrolytes are also absorbed in the ileum. The ileum is the principal source of absorption of bile acids; vitamin B12; and the fat- soluble vitamins A, D, E, and K. Removal of most of the ileum results in vitamin B12 and fat-soluble vitamin deficiencies and diarrhea. The diarrhea is from both the large volume of fluid passed into the colon (large intestine), and the unabsorbed bile salts can cause the colon to release water. Loss of these bile salts can also result in a decrease in fat absorption since the bile salts help the intestine to absorb fats.

The ileocecal valve (valve between the small and large intestine) slows the progress of intestinal fluids into the colon. It also increases the pressure gradient between the ileum and the colon to prevent the colon fluids with high concentrations of bacteria from moving back up into the small intestine.

Removal of the large intestine has minimal effect on digestion and absorption. The colon is the site of absorption of fluid and sodium and the excretion of potassium and bicarbonate. In SBS, the presence of the colon is of value because it increases the absorption of fluids and electrolytes (normal chemicals in the blood stream such as sodium, potassium, chloride, and bicarbonate) and decreases diarrhea.

Adaptation of the Intestine
Loss of a significant amount of the small intestine produces changes in the bowel called intestinal adaptation. The result is an increase in the intestinal surface area of the inside lining (mucosa) of the intestine and an increase in absorption and digestion. The inside lining of the intestine is made of strands of mucosa (villi) that increase the surface area. (Figure 2) 

Figure 2. The Biarchi procedure for making the intestine longer. The enlarged, dilated intestine is divided down the middle after the blood vessels feeding it are separated to one side or the other. The ends are then hooked up. The enlarged intestine now becomes longer and fairly normal in ....

The first and most significant adaptive change is an increase in growth of the villi. The villi are longer and thicker. The inside diameter of the intestine also increases. However, there is only so much increase in diameter of intestine and size of the villi that can occur. A number of growth factors and other still undefined factors are responsible for causing this adaptation. The most important site of adaptation is the small intestine; however, enlargement of the villi also occurs in the large intestine, resulting in an increase in water and electrolyte absorption.

Although the specific mechanisms that cause adaptation are not known, there is information on factors that influence adaptation. (Table 3) Providing enough calories to support growth and development is important. The villi get smaller in patients getting calories only from TPN exclusively. This condition can be reversed by feeding small amounts of nutrition into the stomach or intestines, typically referred to as trophic feeds. 

Table 3: Factors Influencing Intestinal Adaptation

Factors in the bloodstream Hormones (gastrin, cholecystokinin, glucagon) Intestinal factors (e.g., epidermal growth factor, hepatocyte growth factor, glucagon-like peptide-2, interleukin-11)

Gastrointestinal (stomach, intestine) secretions Pancreatic secretions Intestinal secretions Bile

Nutrients in the intestine From outside sources (food) From within the intestine

Normal secretions in the gastrointestinal (stomach and intestines, GI) tract increase adaptation. Bile duct and pancreatic secretions help the small intestine mucosa grow.

Perhaps the most important influence on intestinal adaptation is hormones, growth factors, or cytokines. At present, the only substances that have reached clinical trials are human growth hormone and glucagon-like peptide-2 (GLP-2). There is not yet enough data to determine if these substances increase adaptation of the intestine.

The means by which cells of the mucosa adapt is still unclear. There is increasing evidence that putrescine, spermidine, and spermine may play a crucial role. Experimentally, massive removal of the small bowel results in an increase in these “polyamines” and the enzyme that controls polyamine synthesis, ornithine decarboxylase (ODC). If ODC is blocked after small bowel removal, polyamine concentrations are markedly reduced, and increase in the size of the villi and the mucosal cells does not occur.

Management of Short Bowel Syndrome
In the early period after intestinal loss, attention is directed toward keeping the fluids and electrolytes in the body normal. TPN (food delivered into the bloodstream) is begun. Excess secretions, which are lost through stomas or diarrhea, must be replaced. Blood levels of calcium, magnesium, trace elements, and vitamins and blood pH (acid) must be monitored. Fat (40% of calories) is given into the bloodstream daily or at least three times per week.

As soon as GI function has returned, intestinal feeds are introduced gradually. This is usually accomplished through a gastrostomy (feeding tube placed directly in the stomach) or nasogastric tube (tube placed through the nose into the stomach). Infants and young children must be fed at least in part orally, however, to establish their ability to suck and eat. Because adaptation begins early after loss of intestine, small amounts of feeds are started early to stimulate adaption of the intestine. Small volumes of liquid feedings are introduced first. A trial-and-error method maximizes the results.

Use of elemental diets (where all the nutrients are broken down into simplified forms that can be easily absorbed) have become increasingly popular to feed patients with SBS. These diets have the advantage of being better absorbed. However, more complex diets are more trophic (promoting growth) to the GI tract and help increase adaptation. The decision to use one formula over the other depends on each individual child.

Most diets that are well-tolerated with SBS contain peptides as the major protein source and forms of glucose as the sugar source. Long-chain triglycerides and short-chain fatty acids are important and should be added gradually to the diet because they stimulate mucosal growth. In the past, patients were not fed complex fats because of the fear of increasing diarrhea. Several clinical studies have shown that this is incorrect. One type of fat, medium-chain triglycerides, are absorbed readily through the intestine.

The volume and complexity of feedings are increased gradually. Consideration should be given to adding fiber to the diet, particularly pectin. Vitamins B12, A, D, E, and K may be required. As more nutrients are absorbed, the amount of TPN that is given is decreased. During hospitalization and at home, stools should be monitored periodically for reducing substances which indicate that sugars are not being absorbed, amount of water, frequency of stools, volume, and the presence of undigested fat.

Medications Used for Small Bowel Syndrome

Reducing Stomach Acid Output
There is evidence that gastric (stomach) hypersecretion (making too many secretions) complicates the first phase of adaptation to the SBS. In addition to aggressive monitoring and replacement of fluid and electrolyte losses, early medical treatment should address this problem. In the early postoperative period, antacids or sucralfate may be given via a nasogastric tube (and later by mouth) to reduce the elevated risk of ulcer disease. Cimetidine or ranitidine (Zantac) can be especially useful in decreasing water and sodium losses related to the hypersecretion. Clinically, we typically use cimetidine in doses of 10 to 20 mg/kg/day orally or intravenously divided every 6 hours. If a stronger medicine is required to reduce stomach output, proton-pump inhibitors such as omeprazole (Prilosec) can be used. Oral and intravenous omeprazole have been shown to decrease stool weight and sodium losses in SBS patients. In children, omeprazole can be given, 0.6 to 0.7 mg/kg once or twice daily.

Antimotility and Antisecretory Agents
Medications that slow peristalsis (pushing of food along by the intestines) and increase the time that it takes for food to get through the intestine (transit time) have been used for several decades to treat SBS. By prolonging transit time, there is a longer contact time between nutrients and the cells using the intestine (mucosa), allowing for better absorption and less diarrhea.

Loperamide hydrochloride is one such medicine that weakens transit time in the small bowel and colon. In children, this agent is safely administered with few side effects.

Diphenoxylate (Lomotil) is another antidiarrhea medicine that is well absorbed. It contains atropine to discourage drug abuse by producing undesirable side effects at higher doses. Because diphenoxylate in children has been linked to cases of serious brain, breathing, or heart side effects it is important to use this medication cautiously.

As feedings into the stomach or intestine are gradually increased, if a second medicine is required in addition to loperamide, it is possible to add another drug, such as codeine (0.5 to 1.0 mg/kg per dose orally every 6 hours) to slow small intestine peristalsis further. Tincture of opium (Paregoric) also may be effective and has the benefit of easily being slowly increased just a few drops at a time to achieve the desirable effects, while minimizing the risk of side effects.

The treatment plan should be individualized for each patient based on the length of the remaining intestine, the presence of the ileocecal valve, and the length of the colon. Treating SBS patients, especially patients lacking an ileocecal valve, with antimotility agents may increase the risk of bacterial overgrowth in poorly functioning, dilated enlarged portions of intestine. Diagnosis of bacterial overgrowth in patients experiencing increased pain and diarrhea means that these intestinal slowing medicines should be stopped and a course of antibiotics (usually oral metronidazole) should be started.

The absence of the terminal ileum (last part of the small intestine) increases diarrhea as a result of the high concentration of bile salts and acids which make it to the colon. This is because most of these bile salts and acids are absorbed by the last portion of the small intestine. Colonic bacteria change the bile salts, which stimulates the secretion of water and electrolytes into the colon (large intestine). Agents that bind bile acid, such as cholestyramine, can be effective in treating diarrhea when bile salts and acid are a problem.

Somatostatin is a hormone that inhibits a number of functions of the GI system. Somatostatin and its synthetic version, octreotide, can decrease the formation of gastric acid, decrease how fast food empties from the stomach, and reduce gallbladder contraction, pancreas function, bowel motility, and small intestinal secretions.

Increasing the time it takes for food to move all the way through the intestines (intestinal transit time), and reducing intestinal secretions can result in improved absorption of food, decreased loss of fluids and electrolytes, and is thought to be the mechanism by which somatostatin is beneficial.

Somatostatin and octreotide have been shown to decrease intestinal fluid losses in SBS patients. Because octreotide has a long duration of action and may be given via injections into the fat under the skin, it has been proposed as a potential long-term treatment to improve the lifestyle of SBS patients. Its use in this population has not been studied extensively, however, and the mechanism by which somatostatin benefits patients with SBS is unclear.

It is important to recognize that octreotide can cause possible side effects of abdominal pain, nausea, increased incidence of gallstones, facial flushing, and headache. At this time, the role of octreotide in managing SBS patients seems limited. However, patients whose intestinal output is greater than their oral intake can benefit from the administration of octreotide.

Glutamine and Growth Hormone (GH)
Glutamine and GH, as individual agents and when used together, have been extensively studied in humans with SBS. Glutamine is an energy source for the mucosa (lining of the gut). Experiments have shown that glutamine stimulates the intestinal cells to grow. Adding glutamine to parenteral nutrition encourages the mucosa to grow following massive small bowel removal.

Administration of GH has been shown to increase bowel growth in animal studies. GH also has been shown to induce small bowel lengthening in newborn piglets.

However, five studies of growth hormone use in humans have been performed with mixed results. Human GH is approved by the U.S. Food and Drug Administration for SBS. However, it is unclear if the drug is effective.

Numerous animal studies of epidermal growth factor (EGF) and insulin-like growth factor (IGF-1) suggest that these factors stimulate intestinal adaptation in patients with SBS. EGF is a hormone secreted by the salivary glands and some of the cells of the small intestine. Numerous studies have shown that hepatocyte growth factor (HGF) is also a powerful growth factor for the small intestine. Future clinical trials are necessary to study the roles of these and other growth factors as potential treatments for SBS.

Two substances probably have the greatest potential as growth factors for the small intestine. GLP-2 belongs to a specific class of compounds called proglucagon-derived peptides. Studies have shown that GLP-2 and GLP-2α increase growth of the mucosa and absorptive function in rats. Preliminary studies in adults also support its possible role in the treatment of SBS. Clinical trials are now under way to evaluate the role of GLP-2 in patients with SBS. No trials have yet to be performed in children.

Continued research may allow clinicians to employ growth factors to definitively treat SBS.

Surgery
Reduction of transit time of food through the intestines: A number of surgical techniques have been used to slow transit time or to increase the mucosal surface area for improved absorption. These include turning a portion of the intestine backwards so that it impedes forward motion of the intestinal contents, and creating recirculating loops – both of which have fallen into disfavor. The creation of an artificial ileocecal valve, however, may reduce transit time and may have some benefit to the patient.

Small Intestine Tapering: Removing some of the extra portions of the dilated (enlarged) small intestine prevents the intestinal fluid from sitting in a big piece of intestine like a cesspool (stasis) and bacterial overgrowth (the bacteria flourish in the “cesspool”) and malabsorption. By reducing bacterial overgrowth, bloodstream infection also may be decreased. This procedure has been used frequently. It has allowed some patients to be able to eat fully and to discontinue TPN, but the results reported have not been uniformly good.

Intestinal Lengthening: Two methods are now available to lengthen the intestine. Bianchi originally described intestinal lengthening. Because the blood vessels leading to the intestine separate and course to either side of the intestine, the blood vessels and the intestines that they feed can be separated (Figure 2). So, the enlarged (dilated) small intestine can be split into two parallel portions, each with its own blood supply. This reduces the size of the dilated intestine by half and doubles its length. An intestinal stapling device helps to divide the intestine. A few successful cases have been reported in which the patients have been able to fully eat after this operation with a decrease in infection.

Figure 3. The STEP procedure. A staple which divides the intestine after stapling either side is used to make an “accordion” of the intestine that makes it longer and a fairly normal size.

More recently a STEP (serial transverse enteroplasty) procedure has been used (Figure 3). This procedure can also lengthen the intestine. For both of these operations the intestine must be enlarged. Risks include infection, narrowing of the intestine and redevelopment of a dilated intestine.

Intestinal Pacing: Pacing of the small intestine by electrodes implanted in the gut slows intestinal transit time and increases the time that the food is in contact with the lining of the intestine. This procedure has been effective in the treatment of experimental SBS, but there are no reported clinical cases.

Small Intestine Transplantation: Small intestine failure or inadequate intestinal length leads to the indications for small intestine transplantation in (1) patients with SBS, (2) patients who are unable to be maintained on intestinal feedings and who are developing liver disease as a result of needing to use TPN, or (3) patients who have problems with having a place to get the TPN into the veins so that TPN is no longer possible. Improved immunosuppressive medications, which include tacrolimus and cellcept, as well as a better means of identifying rejection of the intestine, have improved survival.

The complications of small intestine failure are numerous. Infections (in large part from bacteria passing through the intestine into the bloodstream), lymphoproliferative disease (overgrowth of white blood cells) from the effects of aggressive immunosuppression, and bouts of rejection are common and life-threatening.

Rejection is a major issue in small intestine failure. Differentiating between infection and rejection can be difficult. Small intestine transplant biopsy remains the standard, but this can be wrong. Also, interpretation of what constitutes histologic evidence of rejection has changed.

A report from the University of Pittsburgh indicated a 1-year graft and patient survival of 60 to 70%. However, long-term results may well be much lower. Patients surviving small intestine failure were free of TPN in 92% of cases. In the pediatric age group, small intestine transplant was more successful. This was not true for infants younger than age 2 years, however. Rejection occurred in 92% of patients. Because the incidence of death occurring while on the waiting list is still 50%, in some patients isolated liver transplants have been done.

Prognosis
Numerous series of SBS patients have been reported with survivals ranging from 50% to 80%. Adaptation did not seem to be related to the presence or absence of the ileocecal valve or even a particular length of intestine unless it was 20 cm of small intestine or less.

The management of SBS has changed considerably since the 1970s. Before TPN there was little hope for survival. Current, the modalities discussed offer an acceptable-to-good quality and quantity of life. TPN provides appropriate caloric needs. Improved feeding formulas can help to increase the absorptive ability of the small intestine, and surgical procedures, especially intestinal lengthening, may maximize intestinal absorption.

The results of small intestine transplant are improving, and when indicated, this procedure offers an acceptable option. The most promising approach for the future is the use of growth factors to stimulate growth of the intestinal cells and to improve their ability to absorb nutrients. Because most SBS patients adapt within 2 years after resection, ample time should be allowed for adaptation to occur before small intestine transplant is considered.

Full article found here.

Immunization Schedule Interactive Tool

Get the best protection for your child—make sure your child is immunized on schedule. For a complete list of recommended immunizations, just select your child’s birth date.

Based on Immunization Schedule for Children 0 through 6 Years of age

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Neonatal Hemochromatosis Gestational Treatment Studies

Gestational treatment to prevent recurrent lethal neonatal hemochromatosis

Neonatal hemochromatosis (NH) is characterized as a condition in which fetuses and infants under one month of age have accumulation of iron in the liver and other tissues in a pattern similar to that seen in hereditary hemochromatosis. Most cases result in stillbirths, and the average life expectancy of children born with this disease is less than a few days. Death results mainly from liver failure. However, some affected babies have been successfully treated by medical means (with survival reported to be less than 20%) and by liver transplantation (survival reported to be less than 50%).

It has become very clear that NH causes damage to the fetal liver, which usually starts at 20-24 weeks of pregnancy. Considering all known causes of fetal disease, NH has been thought to possibly be the result of a genetic disease (gene defect). However, some curious findings in NH are hard to explain in this way. A mother may have one or more unaffected children before having the first affected child. Thereafter, the following pregnancies may end in either a late stillbirth or a child born with NH. Also, mothers have given birth to affected children with different fathers. The point is: there is no concrete evidence that NH is inherited through genes.

Treatment

We have developed a theory concerning the cause of NH upon which we have based the treatment of prospective mothers who have had children with NH. We believe that the cause of recurrent NH involves certain women developing an abnormal immune response to their unborn babies (called alloimmunity). According to this theory, the mother's immune system mounts an attack against a fetal liver protein and results in liver damage and a direct or indirect effect on fetal iron storage.

Several years ago we began to treat pregnant women on a research protocol. The purpose of treatment is to limit the elaboration of immunoglobulin (mother's immune attack) directed against the fetus (baby). The results of treatments performed as of August 2005 are: 26 women have been treated though 29 pregnancies, all of which ended in a live and reasonably healthy baby. About 75% of the babies showed some evidence of being affected, but only about 15% had significant liver disease. All 29 babies survived with medical care alone (no liver transplant). This is significantly different from these same women's prior affected pregnancies when treatment was not given in which there was only about 10% survival with medical therapy.

Long-term outlook

The results suggest that the course of the pregnancies was altered by the treatment to permit the birth of children with much milder NH and no pregnancy or newborn deaths. These findings suggest that a simple therapy might prevent this devastating disease. Further study is underway to confirm these results.

Full article here.

Toxoplasmosis, Congenital

Congenital toxoplasmosis is caused by transplacental acquisition of Toxoplasma gondii. Signs, if present, are prematurity, intrauterine growth restriction, jaundice, hepatosplenomegaly, myocarditis, pneumonitis, rash, chorioretinitis, hydrocephalus, intracranial calcifications, microcephaly, and seizures. Diagnosis is by serology. Treatment is with pyrimethamine, sulfadiazine, and leucovorin.

Toxoplasma gondii, a parasite found worldwide, causes congenital infection in about 1/10,000 to 80/10,000 births.

Etiology

With rare exception, congenital toxoplasmosis is due to a primary maternal infection during pregnancy. Infection with T. gondii occurs primarily from ingestion of inadequately cooked meat containing cysts, or ingestion of oocysts derived from cat feces. The rate of transmission to the fetus is higher in women infected later during pregnancy. However, those infected earlier in gestation generally have more severe disease. Overall, 30 to 40% of women infected during pregnancy will have a congenitally infected child.

Symptoms and Signs

Pregnant women infected with T. gondii generally do not have clinical manifestations. Similarly, infected neonates are usually asymptomatic at birth, but manifestations may include prematurity, intrauterine growth restriction, jaundice, hepatosplenomegaly, myocarditis, pneumonitis, and various rashes. Neurologic involvement, often prominent, includes chorioretinitis, hydrocephalus, intracranial calcifications, microcephaly, and seizures.

Diagnosis

Serology is important in diagnosing maternal and congenital infection; there are numerous tests, some of which are performed only in reference laboratories. The most reliable are the Sabin-Feldman dye test, the indirect fluorescent antibody (IFA) test, and the direct agglutination assay. Acute maternal infection is suggested by seroconversion or a ≥ 4-fold rise between acute and convalescent IgG titers. However, maternal IgG antibodies may be detectable in the infant through the 1st year. PCR analysis of fetal blood and amniotic fluid may prove a better method. Tests to isolate the organism include inoculation into mice and tissue culture.

In suspected congenital toxoplasmosis, serologic tests, MRI or CT imaging of the brain, CSF analysis, and a thorough eye examination by an ophthalmologist should be performed. CSF abnormalities include xanthochromia, pleocytosis, and increased protein concentration. The placenta is inspected for characteristic signs of T. gondii infection. Nonspecific laboratory findings include thrombocytopenia, lymphocytosis, monocytosis, eosinophilia, and elevated transaminases.

Congenital Toxoplasmosis

Prognosis and Treatment

Some have a fulminant course with early death, whereas others have long-term neurologic sequelae. Occasionally, neurologic manifestations (eg, chorioretinitis, mental retardation, deafness, seizures) develop years later in children who appeared normal at birth. Consequently, children with congenital toxoplasmosis should be closely monitored beyond the neonatal period.

Limited data suggest that treatment of infected women during pregnancy may be beneficial to the fetus.  Spiramycin 


(available in the US from the FDA) has been used to prevent maternofetal transmission.  Pyrimethamine and sulfonamides have been used later in gestation to treat the infected fetus.

Treatment of symptomatic and asymptomatic neonates may improve outcome. Therefore, treatment with Pyrimethamine (initial loading dose of 2 mg/kg po once/day for 2 days followed by 1 mg/kg po once/day, maximum 25 mg, sulfadiazine (42.5 to 50 mg/kg po bid, maximum 4 g), and leucovorin (10 mg po 3 times/wk) is recommended. After the initial 6 mo of treatment, sulfadiazine and leucovorin are continued as previously but the pyrimethamine is administered less frequently (only on Mon-Wed-Fri).  All treatment should be monitored by an expert.  The use of corticosteroids is controversial and should be determined case by case.

Prevention

Pregnant women should avoid contact with cat litter boxes and other areas contaminated with cat feces. Meat should be thoroughly cooked before consumption, and hands should be washed after handling raw meat or unwashed produce. Women at risk for primary infection should be screened during pregnancy. Those infected during the 1st or 2nd trimester should be counseled regarding available treatments.

Full article found here.

Herpes Simplex Virus (HSV) Infection in Neonates

Neonatal herpes simplex virus infection is usually transmitted during labor and/or delivery. Signs are typically a vesicular eruption and subsequent disseminated disease. Diagnosis is by viral culture, histology, serology, or molecular biology. Treatment is with high-dose parenteral acyclovir and supportive care.

Neonatal herpes simplex virus (HSV) infection has high mortality and significant morbidity. Incidence estimates range from 1/3,000 to 1/20,000 births. HSV type 2 causes about 80% of cases; 20% are caused by HSV type 1.

HSV is usually transmitted during delivery through an infected maternal genital tract. Transplacental transmission of virus and hospital-acquired spread from one neonate to another by hospital personnel or family may account for about 15% of cases. Mothers of neonates with HSV infection tend to have no history or symptoms of genital infection at the time of delivery.

Symptoms and Signs

Manifestations generally occur between the 1st and 2nd wk of life but may not appear until as late as the 4th wk. Patients may present with local or disseminated disease. Skin vesicles are common in either form, occurring in about 55% overall. Those with no skin vesicles usually present with localized CNS disease. In patients with isolated skin or mucosal disease, progressive or more serious forms of disease frequently follow within 7 to 10 days if left untreated.

Neonatal Herpes Simplex Infection

Neonates with localized disease can be divided into 2 groups. One group has encephalitis manifested by neurologic findings, CSF pleocytosis, and elevated protein concentration, with or without concomitant involvement of the skin, eyes, and mouth. The other group has only skin, eye, and mouth involvement and no evidence of CNS or organ disease.

Neonates with disseminated disease and visceral organ involvement have hepatitis, pneumonitis, and/or disseminated intravascular coagulation with or without encephalitis or skin disease.

Other signs, which can occur singly or in combination, include temperature instability, lethargy, hypotonia, respiratory distress, apnea, and seizures.

Diagnosis

Rapid diagnosis by viral culture or HSV PCR is essential. The most common site of retrieval is skin vesicles. The mouth, eyes, and CSF are also high-yield sites. In some with encephalitis, virus is found only in the brain. Diagnosis also can be made by neutralization with appropriate high-titer antiserum; immunofluorescence of lesion scrapings, particularly with use of monoclonal antibodies; and electron microscopy. If no diagnostic virology facilities are available, a Papanicolaou test of the lesion base may show characteristic multinucleated giant cells and intranuclear inclusions, but this procedure is less sensitive than culture, and false-positives also occur.

Prognosis

The mortality rate of untreated disseminated disease is 85%; among those with untreated local disease and encephalitis, it is about 50%. At least 95% of survivors have severe neurologic sequelae. Death is uncommon in those with local disease but without CNS or organ disease, except as the result of concomitant medical problems, but about 30% develop neurologic impairment, which may not manifest until 2 to 3 yr of age.

Treatment

Acyclovir decreases the mortality rate by 50% and increases the percentage of children who develop normally from 10 to 50%; dose is 20 mg/kg IV q 8 h for 14 to 21 days. Vigorous supportive therapy is required, including appropriate IV fluids, alimentation, respiratory support, correction of clotting abnormalities, and control of seizure disorders. Herpetic keratoconjunctivitis requires concomitant systemic acyclovir 


and topical therapy with a drug such as trifluridine.

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Meningitis, Neonatal

Neonatal meningitis is inflammation of the meninges due to bacterial invasion in the 1st 90 days of life. Signs are those of sepsis, CNS irritation—lethargy, seizures, vomiting, irritability, nuchal rigidity, a bulging or full fontanelle—and cranial nerve abnormalities. Diagnosis is by lumbar puncture. Treatment is with antibiotics.

Neonatal meningitis occurs in 2/10,000 full-term and 2/1,000 low-birth-weight (LBW) neonates, with a male predominance. It occurs in about 25% of neonates with sepsis and occasionally occurs in isolation.

Etiology

Group B streptococcus (GBS—predominantly type III), Escherichia coli (particularly those strains containing the K1 polysaccharide), and Listeria monocytogenes account for 75% of neonatal meningitis.

Enterococci, nonenterococcal group D streptococci, α-hemolytic streptococci, and other gram-negative enteric organisms (eg, Klebsiella sp, Enterobacter sp, Citrobacter diversus) also are important pathogens. Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae have been reported as causes.

Neonatal meningitis most frequently results from the bacteremia that occurs with neonatal sepsis; the higher the colony count in the blood culture, the higher is the risk for meningitis. Meningitis may also result from scalp lesions, particularly when developmental defects lead to communication between the skin surface and the subarachnoid space, which predisposes to thrombophlebitis of the diploic veins. Rarely, there is direct extension to the CNS from a contiguous otic focus (eg, otitis media).

Symptoms and Signs

Frequently, only those findings associated with neonatal sepsis (eg, temperature instability, respiratory distress, jaundice, apnea) are manifest. CNS signs (eg, lethargy, seizures [particularly focal], vomiting, irritability) more specifically suggest meningitis. A bulging or full fontanelle occurs in about 25% and nuchal rigidity in only 15%. Cranial nerve abnormalities (particularly those involving the 3rd, 6th, and 7th nerves) may also be present.

Meningitis due to GBS may occur in the 1st wk of life, accompanying early-onset neonatal sepsis and frequently presenting as a pneumonic illness. Usually, however, GBS meningitis occurs after this period (most commonly in the 1st 3 mo of life) as an isolated illness characterized by absence of antecedent obstetric or perinatal complications and the presence of more specific signs of meningitis (eg, fever, lethargy, seizures).

Ventriculitis frequently accompanies neonatal meningitis, particularly when caused by gram-negative enteric bacilli. Organisms that cause meningitis together with severe vasculitis, particularly C. diversus and Enterobacter sakazakii , are likely to produce cysts and abscesses. Pseudomonas aeruginosa , E. coli K1, and Serratia sp also may cause brain abscesses. An early clinical sign of brain abscess is increased intracranial pressure (ICP), commonly manifested by vomiting, a bulging fontanelle, and sometimes enlarging head size. Deterioration in an otherwise stable neonate with meningitis suggests progressive increased ICP increase from abscess or hydrocephalus, or rupture of an abscess into the ventricular system.

Diagnosis

Definitive diagnosis is made by CSF examination via lumbar puncture (LP), which should be performed in any neonate suspected of having sepsis or meningitis. However, LP can be difficult to perform in a neonate, and there is some risk for hypoxia. Poor clinical condition (eg, respiratory distress, shock, thrombocytopenia) makes LP risky. If LP is delayed, the neonate should be treated as though meningitis were present. Even when the clinical condition improves, the presence of inflammatory cells in CSF and abnormal chemistries days after illness onset can still suggest the diagnosis. A needle with a trocar should be used for LP to avoid introducing epithelial rests and subsequent development of epitheliomas. The CSF, even if bloody or acellular, should be cultured. About 15% of neonates with negative blood cultures have positive CSF cultures. LP should be repeated at 24 to 48 h if clinical response is questionable and at 72 h when gram-negative organisms are involved (to ensure sterilization). Some experts believe that a repeat LP at 24 h in neonates with GBS meningitis has prognostic value. LP should not be repeated at the end of therapy if the neonate is doing well.

Normal CSF values are controversial and age-related. In general, for LBW infants up to 4 wk of age, 40 WBCs/μL (1⁄2 of which may be PMNs), a protein level of 220 mg/dL, and a glucose level of 50 mg/dL (2.8 mmol/L) are considered the upper limits of normal. For term infants, these limits are 20 WBCs/μL (with 1⁄2 PMNs), a protein level of 170 mg/dL, and a glucose level of 50 mg/dL (2.8 mmol/L). The CSF glucose concentration depends largely on serum glucose concentration and may normally be as low as 20 to 30 mg/dL (1.1 to 1.7 mmol/L), therefore, serum glucose should be measured before LP so the ratio of CSF:serum glucose levels can be determined (< 50% is abnormal).

Ventriculitis is suspected in a neonate not responding appropriately to antimicrobial therapy. The diagnosis is made when a ventricular puncture yields a WBC count greater than that from the LP, Gram stain or culture is positive, ventricular pressure is increased, and ventricles are dilated. When ventriculitis or brain abscess is suspected, an MRI or CT scan with contrast may aid diagnosis.

Prognosis

Without treatment, the mortality rate from neonatal meningitis approaches 100%. With treatment, prognosis is determined by birth weight, organism, and clinical severity. Mortality rate for gram-negative neonatal meningitis is 20 to 30% and for gram-positive (eg, GBS), 10 to 20%. For organisms that produce vasculitis, meningitis, and brain abscess (necrotizing meningitis), the mortality rate may approach 75%. Neurologic sequelae (eg, hydrocephalus, hearing loss, mental retardation) develop in 20 to 50% of infants who survive, with a poorer prognosis when gram-negative enteric bacilli are the cause.

Prognosis also depends partly on the number of organisms present in CSF at diagnosis. The duration of positive CSF cultures correlates directly with the incidence of complications. In general, CSF cultures from neonates with GBS are usually sterilized within the 1st 24 h of antimicrobial therapy. Those from gram-negative bacillary meningitis remain positive for an average of 3 1⁄2 days.

GBS meningitis has a mortality rate significantly lower than that of early-onset GBS sepsis.

Treatment

Empiric treatment is begun with ampicillin plus cefotaxime. Hospitalized neonates who previously received antibiotics (eg, for early-onset sepsis) may have resistant organisms; fungal disease may also be considered in a septic-appearing neonate after prolonged hospitalization. Until the diagnosis of meningitis is confirmed, ill neonates with hospital-acquired infection should initially receive vancomycin plus an aminoglycoside different from the one previously used, or a 3rd-generation cephalosporin. Antibiotics are adjusted when results of the LP are available and culture and sensitivities are known.

The recommended initial treatment for GBS meningitis in neonates < 1 wk of age is penicillin G
100,000 to 150,000 units/kg IV q 8 h or ampicillin 100 mg/kg IV q 8 h, plus gentamicin 2.5 mg/kg IV q 8 h. If clinical improvement occurs or sterilization of CSF is documented, gentamicin Some can be stopped.

For enterococci or L. monocytogenes, treatment is generally ampicillin plus gentamicin.

In gram-negative bacillary meningitis, treatment is difficult. The traditional regimen of ampicillin
plus an aminoglycoside results in a 20 to 30% mortality rate, with a high rate of sequelae in survivors. A 3rd-generation cephalosporin should be strongly considered in neonates with proved gram-negative meningitis (or sepsis) or those convincingly septic. If antibiotic resistance is a concern, both an aminoglycoside and a 3rd-generation cephalosporin may be used until sensitivities are known. However, these drugs are generally not used routinely, because certain gram-negative organisms are induced to produce β-lactamase by 3rd-generation cephalosporins, resulting in rapid development of resistance.

Parenteral therapy for gram-positive meningitis is given for a minimum of 14 days, and for complicated gram-positive or gram-negative meningitis, a minimum of 21 days.

Because meningitis may be considered part of the continuum of neonatal sepsis, the adjunctive measures used in treating neonatal sepsis (see Infections in Neonates: Other treatment) should also be used in neonatal meningitis. Patients should be closely followed for neurologic complications during the 1st 2 yr of life.

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