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NEC • NEC is the most common life-threatening emergency of the gastrointestinal tract in the newborn period. • Cause is unknown • I/n.1_5% • Because very small, ill preterm infants are particularly susceptible to NEC, a rising incidence may reflect improved survival of this high-risk group of patients. • Pathology and Pathogenesis • Many factors may contribute to the development of a necrotic segment of intestine, gas accumulation in the submucosa of the bowel wall (pneumatosis intestinalis), and progression of the necrosis to perforation, peritonitis, sepsis, and death.
The distal part of the ileum and the proximal segment of colon are involved most frequently; • The triad of intestinal ischemia (injury), enteral nutrition (metabolic substrate), and bacterial translocation has classically been linked to NEC. • The greatest risk factor for NEC is prematurity. • results from an interaction between loss of mucosal integrity due to (ischemia, infection, inflammation) and the host's response to that injury (circulatory, immunologic, inflammatory), leading to necrosis of the affected area. • Has Coagulation necrosis. • Clustering of cases suggests a primary role for an infectious agent. • Various bacterial and viral agents, including Escherichia coli, Klebsiella, Clostridium perfringens, Staphylococcus epidermidis,astrovirus, norovirus, and rotavirus, have been recovered from cultures.
Aggressive integral feeding other than breast milk predispose to the development of NEC. • 90% in premature infant ,but also in full term with a history of birth asphyxia, Down syndrome, congenital heart disease, rotavirus infections, and Hirschsprung disease. Clinical Manifestations The onset of NEC is usually in the 2nd or 3rd week of life but can be as late as 3 mo in VLBW infants. Age of onset is inversely related to gestational age. The 1st signs may be nonspecific, including lethargy and temperature instability, or related to gastrointestinal pathology, such as abdominal distention and gastric retention.
bloody stools are seen in 25% of patients. • Because of nonspecific signs, sepsis may be suspected before NEC. • The spectrum of illness is broad, ranging from mild disease with only guaiac-positive stools to severe illness with bowel perforation, peritonitis, systemic inflammatory response syndrome, shock, and death. • Progression may be rapid, but it is unusual for the disease to progress from mild to severe after 72 hr.
Table 96-1 -- SIGNS AND SYMPTOMS ASSOCIATED WITH NECROTIZING ENTEROCOLITIS
Diagnosis • Plain abdominal radiographs are essential to make a diagnosis of NEC. • The finding of pneumatosis intestinalis (air in the bowel wall) confirms the clinical suspicion of NEC and is diagnostic; • 50-75% of patients have pneumatosis when treatment is started. • Portal venous gas is a sign of severe disease, and pneumoperitoneum indicates a perforation. • Hepatic ultrasonography may detect portal venous gas despite normal abdominal roentgenograms.
hepatic portal venous gas & pneumatosis intestinalis are thought to be pathognomonic for neonatal necrotizing enterocolitis. • The differential diagnosis of NEC includes specific infections (systemic or intestinal), gastrointestinal obstruction, volvulus, and isolated intestinal perforation. • Idiopathic focal intestinal perforation can occur spontaneously or after the early use of postnatal steroids and indomethacin. • Pneumoperitoneum develops in such patients, but they are usually less ill than those with NEC.
Treatment • Rapid initiation of therapy is required with ABC of life 1st . no definitive treatment for established NEC, so, therapy is directed at giving supportive care and preventing further injury with cessation of feeding, nasogastric decompression, and administration of intravenous fluids. Careful attention to respiratory status, coagulation profile, and acid-base and electrolyte balances are important. Remove umbilical catheter. BroadspectrumAbc s. Ventilation with intra nasal o2 Send blood culture and correction of hematologic, metabolic, and electrolyte abnormalities are essential to stabilize the infant with NEC. Treatment
Follow vital signs • Then sequential anteroposterior and cross-table lateral or lateral decubitus abdominal radiographs to detect intestinal perforation; • and serial determinations of hematologic, electrolyte, and acid-base status. • Indications for surgery include evidence of perforation on abdominal roentgenograms (pneumoperitoneum) or positive result of abdominal paracentesis (stool or organism on Gram stain preparation from peritoneal fluid). • Failure of medical management, a single fixed bowel loop on radiographs, abdominal wall erythema, and a palpable mass are relative indications for exploratory laparotomy.
In unstable premature infants with perforated NEC, peritoneal drainage can be cautiously considered as an alternative to exploratory laparotomy, although the best surgical approach in these infants remains unresolved. • The type of surgical operation did not influence survival. • Most require delayed 2ndary laparotomy.
Prognosis • Medical management fails in about 20-40% of patients with pneumatosis intestinalis at diagnosis; of these, 10-30% die. • Early postoperative complications include wound infection, dehiscence, and stomal problems (prolapse, necrosis). • Later complications include intestinal strictures, which develop at the site of the necrotizing lesion in about 10% of surgically or medically managed patients. • Resection of the obstructing stricture is curative. After massive intestinal resection, complications from postoperative NEC include short-bowel syndrome (malabsorption, growth failure, malnutrition), complications related to central venous catheters (sepsis, thrombosis), and cholestatic jaundice. • Premature infants with NEC who require surgical intervention or who have concomitant bacteremia are at increased risk for adverse growth and neurodevelopmental outcome.
Prevention • Newborns exclusively breast-fed have a reduced risk of NEC. • Gut stimulation protocols consisting of minimal enteral feeds followed by judicious volume advancement decreased the incidence of NEC • Prophylactic enteral antibiotics can reduce the risk of NEC, although concerns about adverse outcomes persist, particularly related to the development of resistant bacteria. • Probiotic preparations may also decrease the incidence of NEC; • enteral supplementation of probiotics reduces the risk of severe NEC (stage II or higher) and mortality in preterm infants. • The safety and efficacy of these supplements needs further evaluation in infants <1,000 g birthweight.
Hirschsprung disease • or congenital aganglionic megacolon, is a developmental disorder (neurocristopathy) of the enteric nervous system, characterized by the absence of ganglion cells in the submucosal and myenteric plexus. • It is the most common cause of lower intestinal obstruction in neonates, with an overall incidence of 1 in 5,000 live births. • The male:female ratio for Hirschprung disease is 4 : 1 for short-segment disease and closer to 1 : 1 as the length of the involved segment increase. • Prematurity is uncommon.
There is an increased familial incidence in long-segment disease. • Hirschsprung disease may be associated with other congenital defects, including Down, Goldberg-Shprintzen, Smith-Lemli-Opitz, Shah-Waardenburg, cartilage-hair hypoplasia, and congenital hypoventilation (Ondine's curse) syndromes and urogenital or cardiovascular abnormalities. • Hirschsprung disease has been seen in association with microcephaly, mental retardation, abnormal facies, autism, cleft palate, hydrocephalus, and micrognathia.
Pathology • arrest of neuroblast migration from the proximal to distal bowel. • Without the myenteric and submucosal plexus, there is inadequate relaxation of the bowel wall and bowel wall hypertonicity, which can lead to intestinal obstruction. • Is sporadic ,although familiar auto.domin& recessive….. Also. • Mostly The aganglionic segment is limited to the rectosigmoid in 80% of patients. • Approximately 10% to 15% of patients have long-segment disease, defined as disease proximal to the sigmoid colon. • Total bowel aganglionosis is rare and accounts for approximately 5% of cases • Observed histologically is an absence of Meissner and Auerbach plexus and hypertrophied nerve bundles with high concentrations of acetylcholinesterase between the muscular layers and in the submucosa.
Clinical Manifestations • Hirschsprung disease is usually diagnosed in the neonatal period secondary to a distended abdomen, failure to pass meconium, and/or bilious emesis or aspirates with feeding intolerance. • In 99% of healthy full-term infants, meconium is passed within 48 hr of birth. • Hirschsprung disease should be suspected in any full-term infant (the disease is unusual in preterm infants) with delayed passage of stool. • Some neonates pass meconium normally but subsequently present with a history of chronic constipation. • Failure to thrive with hypoproteinemia from protein-losing enteropathy is a less common presentation because Hirschsprung disease is usually recognized early in the course of the illness. • Breast-fed infants might not suffer disease as severe as formula-fed infants.
Failure to pass stool leads to dilatation of the proximal bowel and abdominal distention. • As the bowel dilates, intraluminal pressure increases, resulting in decreased blood flow and deterioration of the mucosal barrier. • Stasis allows proliferation of bacteria, which can lead to enterocolitis (Clostridium difficile, Staphylococcus aureus, anaerobes, coliforms) with associated diarrhea, abdominal tenderness, sepsis and signs of bowel obstruction. • Early recognition of Hirschsprung disease before the onset of enterocolitis is essential in reducing morbidity and mortality.
Hirschsprung disease in older patients must be distinguished from other causes of abdominal distention and chronic constipation (Table 324-3 and Fig. 324-1). • The history often reveals constipation starting in infancy that has responded poorly to medical management. • Fecal incontinence, fecal urgency, and stool-withholding behaviors are usually not present. • The abdomen is tympanitic and distended, with a large fecal mass palpable in the left lower abdomen. • Rectal examination demonstrates a normally placed anus that easily allows entry of the finger but feels snug.
The rectum is usually empty of feces, and when the finger is removed, there may be an explosive discharge of foul-smelling feces and gas. • The stools, when passed, can consist of small pellets, be ribbon-like, or have a fluid consistency, unlike the large stools seen in patients with functional constipation. • Intermittent attacks of intestinal obstruction from retained feces may be associated with pain and fever. • Urinary retention with enlarged balder or hydronephrosis can occur secondary to urinary compression.
Table 324-3 -- DISTINGUISHING FEATURES OF HIRSCHSPRUNG DISEASE AND FUNCTIONAL CONSTIPATION
In neonates, Hirschsprung disease must be differentiated from meconium plug syndrome, meconium ileus, and intestinal atresia. • In older patients, the Currarino triad must be considered, which includes anorectal malformations (ectopic anus, anal stenosis, imperforate anus), sacral bone anomalies (hypoplasia, poor segmentation), and presacral anomaly (anterior meningoceles, teratoma, cyst).
Diagnosis • Rectal suction biopsy is the gold standard for diagnosing Hirschsprung disease. • The biopsy material should contain an adequate amount of submucosa to evaluate for the presence of ganglion cells. • To avoid obtaining biopsies in the normal area of hypoganglionosis, which ranges from 3 to 17 mm in length, the suction rectal biopsy should be obtained no closer than 2 cm above the dentate line. • The biopsy specimen should be stained for acetylcholinesterase to facilitate interpretation. • Patients with aganglionosis demonstrate a large number of hypertrophied nerve bundles that stain positively for acetylcholinesterase with an absence of ganglion cells.
Anorectal manometry measures the pressure of the internal anal sphincter while a balloon is distended in the rectum. • In normal patients, rectal distention initiates relaxation of the internal anal sphincter in response to rectal distention with a balloon. • In patients with Hirschsprung disease, the internal anal sphincter fails to relax in response to rectal distention. • Although the sensitivity and specificity can vary widely, in experienced hands, the test can be quite sensitive. • The test, however, can be technically difficult to perform in young infants. • A normal response in the course of manometric evaluation precludes a diagnosis of Hirschsprung disease; an equivocal or paradoxical response requires a repeat motility or rectal biopsy.
An unprepared contrast enema is most likely to aid in the diagnosis in children older than 1 mo because the proximal ganglionic segment might not be significantly dilated in the first few weeks of life. • Classic findings are based on the presence of an abrupt narrow transition zone between the normal dilated proximal colon and a smaller-caliber obstructed distal aganglionic segment. • In the absence of this finding, it is imperative to compare the diameter of the rectum to that of the sigmoid colon, because a rectal diameter that is the same as or smaller than the sigmoid colon suggests Hirschsprung disease. • Radiologic evaluation should be performed without preparation to prevent transient dilatation of the aganglionic segment. As many as 10% of newborns with Hirschsprung disease have a normal contrast study.
Twenty-four hour delayed films are helpful in showing retained contrast. If significant barium is still present in the colon, it increases the suspicion of Hirschsprung disease even if a transition zone is not identified. Barium enema examination is useful in determining the extent of aganglionosis before surgery and in evaluating other diseases that manifest as lower bowel obstruction in a neonate. Full-thickness rectal biopsies can be performed at the time of surgery to confirm the diagnosis and level of involvement.
Treatment • definitive treatment is operative intervention. • Previously, a temporary ostomy was placed and definitive surgery was delayed until the child was older. • Currently, many infants undergo a primary pull-through procedure except if there is associated enterocolitis or other complications, when a decompressing ostomy is usually required. • There are 3 basic surgical options. • The first successful surgical procedure, described by Swenson, was to excise the aganglionic segment and anastomose the normal proximal bowel to the rectum 1-2 cm above the dentate line.
The operation is technically difficult and led to the development of 2 other procedures. Duhamel described a procedure to create a neorectum, bringing down normally innervated bowel behind the aganglionic rectum. • The neorectum created in this procedure has an anterior aganglionic half with normal sensation and a posterior ganglionic half with normal propulsion. • The endorectal pull-through procedure described by Soave involves stripping the mucosa from the aganglionic rectum and bringing normally innervated colon through the residual muscular cuff, thus bypassing the abnormal bowel from within. • Advances in techniques have led to successful laparoscopic single-stage endorectal pull-through procedures, which are the treatment of choice.
In ultrashort-segmentHirschsprung disease or internal sphincter achalasia, the aganglionic segment is limited to the internal sphincter. • The clinical symptoms are similar to those of children with functional constipation. • Ganglion cells are present on rectal suction biopsy, but the anorectal manometry is abnormal, with failure of relaxation of the internal anal sphincter in response to rectal distention. Current treatment, although still controversial, includes anal botulism injection to relax the anal sphincter and anorectal myectomy if indicated.
Long-segmentHirschsprung disease involving the entire colon and, at times, part of the small bowel presents a difficult problem. • Anorectal manometry and rectal suction biopsy demonstrate findings of Hirschsprung disease, but radiologic studies are difficult to interpret because a colonic transition zone cannot be identified. • The extent of aganglionosis can be determined accurately by biopsy at the time of laparotomy. When the entire colon is aganglionic, often together with a length of terminal ileum, ileal-anal anastomosis is the treatment of choice, preserving part of the aganglionic colon to facilitate water absorption, which helps the stools to become firm. • The prognosis of surgically treated Hirschsprung disease is generally satisfactory; the great majority of patients achieve fecal continence. • Long-term postoperative problems include constipation, recurrent enterocolitis, stricture, prolapse, perianal abscesses, and fecal soiling. • Some children require myectomy or a redo pull-through procedure.
Seizures are the most important and common indicator of significant neurologic dysfunction in the neonatal period. • Seizure incidence is higher during this period than in any other period in life: 57.5/1,000 in infants with birth weights <1,500 g and 2.8/1,000 in infants weighing between 2,500 and 3,999 g have seizures.
Pathophysiology • The immature brain has many differences from the mature brain that render it more excitable and more likely to develop seizures. • 1.are delay in Na+, K+-ATPase maturation and increased NMDA and AMPA receptor density. In addition, the specific types of these receptors that are increased are those that are permeable to calcium (GLUR2 AMPA receptors), in particularly those resulting from perinatal hypoxia. • 2. delay in the development of inhibitory GABAergic transmission. In fact, GABA in the immature brain has an excitatory function as the chloride gradient is reversed relative to the mature brain, with higher concentrations of chloride being present intracellularly than extracellularly. • This phenomenon appears to be more prominent in male neonates, perhaps explaining their greater predisposition to seizures. The reason for this is that the Cl− transporter, NKCC1, is predominantly expressed in the neonatal period, leading to transport of Cl− into the cell, and to cellular depolarization upon activation of GABAA receptors.
3. Another difference is This is important for neuronal development but renders the neonatal brain hyperexcitable. • With maturation, expression of NCCK1 decreases and KCC2 increases. KCC2 transports Cl− out of the cell, resulting in reduction of intracellular chloride concentration so that when GABAA receptors are activated, Cl− influx and hyperpolarization occur. • Bumetanide, a diuretic that blocks NKCC1, can prevent excessive GABA depolarization and avert the neuronal hyperexcitability underlying neonatal seizures.
But the immature brain appears to be more resistant to the deleterious effects of seizures than the mature brain, as a result of increases in calcium binding proteins that buffer injury-related increases in calcium, increased extracellular space, decreased levels of the second messenger inositol triphosphate, and the immature brain's ability to tolerate hypoxic conditions by resorting to anaerobic energy metabolism. it is difficult in most models and in human studies to distinguish effects of seizures, the underlying disease responsible for the seizures, and, in the case of expedient treatment, the AEDs used to stop the seizures. Most physicians currently believe that it is favorable to control clinical as well as electrographic seizures, but not at the expense of causing severe systemic toxicity from AEDs.
Types of Neonatal Seizures • There are 5 main neonatal seizure types: subtle, clonic, tonic, spasms, and myoclonic. • Spasms, focal clonic or tonic, and generalized myoclonic seizures are, as a rule, associated with electrographic discharges (epileptic seizures), • whereasthe subtle, generalized tonic and other myoclonic seizures are usually not associated with discharges and thus are thought to usually represent release phenomena with abnormal movements secondary to brain injury rather than true epileptic seizures.
To determine clinically whether such manifestations are seizures or release phenomena is often difficult, but precipitation of such manifestations by stimulation and aborting them by restraint or manipulation would suggest that they are not seizures. Performing such maneuvers at the bedside is often helpful. • In addition, continuous bedside EEG monitoring helps make this distinction. Thus, such monitoring is the standard of care in many nurseries. • Subtle Seizures • Subtle seizures include transient eye deviations, nystagmus, blinking, mouthing, abnormal extremity movements (rowing, swimming, bicycling, pedaling, and stepping), fluctuations in heart rate, hypertension episodes, and apnea. Subtle seizures occur more commonly in premature than in full-term infants.
Clonic Seizures • Clonic seizures can be focal or multifocal. Multifocal clonic seizures incorporate several body parts and are migratory in nature. The migration follows a non-Jacksonian trend; for example, jerking of the left arm can be associated with jerking of the right leg. • Generalized clonic seizures, which are bilateral, symmetrical, and synchronous, are uncommon in the neonatal period presumably due to decreased connectivity associated with incomplete myelination at this age. • Tonic Seizures • Tonic seizures can be focal or generalized (generalized are more common). Focal tonic seizures include persistent posturing of a limb or posturing of trunk or neck in an asymmetric way often with persistent horizontal eye deviation. • Generalized tonic seizures are bilateral tonic limb extension or tonic flexion of upper extremities often associated with tonic extension of lower extremities.
Spasms • Spasms are sudden generalized jerks lasting 1-2 sec that are distinguished from generalized tonic spells by their shorter duration and by the fact that spasms are usually associated with a single, very brief, generalized discharge. • Myoclonic Seizures • Myoclonic seizures are divided into focal, multifocal, and generalized types. • Myoclonic seizures can be distinguished from clonic seizures by the rapidity of the jerks and by their lack of rhythmicity. • Focal myoclonic seizures characteristically affect the flexor muscles of the upper extremities and are sometimes associated with seizure activity on EEG.
Multifocal myoclonic movements involve asynchronous twitching of several parts of the body and are not commonly associated with seizure discharges on EEG. Generalized myoclonic seizures involve bilateral jerking associated with flexion of upper and occasionally lower extremities. The latter type of myoclonic jerks is more commonly correlated with EEG abnormalities than the other types. • Seizures vs. Jitteriness • Jitteriness can be defined as rapid motor activities, such as a tremor or shake, that can be ended by flexion or holding the limb. • Seizures, on the other hand, generally do not end with tactile or motor suppression. • Jitteriness, unlike most seizures, is usually induced by a stimulus. Also unlike jitteriness, seizures often involve eye deviation and autonomic changes.
Table 586-14 -- CAUSES OF NEONATAL SEIZURES • AGES 1-4 DAYS
Causes • Hypoxic-Ischemic Encephalopathy • This is the most common cause of neonatal seizures, accounting for 50-60% of patients. Seizures secondary to this encephalopathy occur within 12 hr of birth. • Vascular Events • These include intracranial bleeds and ischemic strokes and account for 10-20% of patients. Three types of hemorrhage can be distinguished: primary subarachnoid hemorrhage, germinal matrix–intraventricular hemorrhage, and subdural hemorrhage. Patients with arterial strokes or venous sinus thrombosis can present with seizure and these can be diagnosed by neuroimaging. Venous sinus thrombosis could be missed unless MR or CT venography studies are requested. • Intracranial Infections • Bacterial and nonbacterial infections account for 5-10% of the cases of neonatal seizures and include bacterial meningitis, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus, herpes simplex virus) infections, particularly herpes simplex encephalitis.
Brain Malformations • Brain malformations account for 5-10% of neonatal seizure cases. An example is Aicardi syndrome, which affects girls and consists of retinal lacunae, agenesis of the corpus callosum, and severe seizures including subsequent infantile spasms with hypsarrhythmia that is sometimes initially unilateral on EEG. • Metabolic Disturbances • Metabolic disturbances include disturbances in glucose, calcium, magnesium, other electrolytes, amino acids, or organic acids and pyridoxine dependency. • Hypoglycemia can cause neurologic disturbances and is very common in small neonates and neonates whose mothers are diabetic or prediabetic. The duration of hypoglycemia is very critical in determining the incidence of neurologic symptoms. • Hypocalcemia occurs at two peaks. The first peak corresponds to low-birthweight infants and is evident in the first 2-3 days of life. The second peak occurs later in neonatal life and often involves large, full-term babies who consume milk that has an unfavorable ratio of phosphorus to calcium and phosphorus to magnesium. Hypomagnesemia is often associated with hypocalcemia. Hyponatremia can cause seizures and is often secondary to inappropriate antidiuretic hormone secretion.
Local anesthetic intoxication seizures can result from neonatal intoxication with local anesthetics administered into the infant's scalp. • Neonatal seizures can also result from disturbances in amino acid or organic acid metabolism. These are usually associated with acidosis and/or hyperammonemia. However, even in the absence of these findings, if a cause of the seizures is not immediately evident, then ruling out metabolic causes requires a full metabolic work-up (Chapter 586.2) including examination of serum amino acids, acyl carnitine profile, lactate, pyruvate, and ammonia, examination of urine for amino acids and organic acids, and examination of CSF for glucose, protein, cells, amino acids, very long chain fatty acids (for neonatal adrenoleukodystropy and Zellweger syndrome), lactate, pyruvate, and perhaps other tests. This is because many inborn errors of metabolism such as nonketotic hyperglycinemia can manifest with neonatal seizures (often mistaken initially for hiccups) and can be detected only by performing these tests. Definitive diagnosis of nonketotic hyperglycinemia, for example, requires measuring the ratio of CSF glycine to plasma glycine. • Pyridoxine and pyridoxal dependency, which are malfunctions of pyridoxine metabolism, can cause severe seizures. These seizures, which are often multifocal clonic, usually start during the first hours of life. Mental retardation is often associated if therapy is delayed (Chapter 586.6).
Drug Withdrawal • Seizures can rarely be caused by the neonate's passive addiction and then drug withdrawal. Such drugs include narcotic analgesics, sedative-hypnotics, and others. The associated seizures appear during the first 3 days of life. • Neonatal Seizure Syndromes • Seizure syndromes include benign idiopathic neonatal seizures (fifth day fits), which are usually apneic and focal motor seizures that start around the fifth day of life. Interictal EEG shows a distinctive pattern called theta pointu alternant (runs sharp 4-7 Hz activity), and ictal EEG shows multifocal electrographic seizures. Patients have a good response to medications and a good prognosis. Autosomal dominant benign familial neonatal seizures have onset at 2-4 days of age and usually remit at 2-15 wk of age. The seizures consist of ocular deviation, tonic posturing, clonic jerks, and, at times, motor automatisms. Interictal EEG is usually normal. These have been shown to be due to mutations in the KCNQ2 and KCNQ3 genes. Approximately 16% of patients develop later epilepsy. Early myoclonic encephalopathy and early infantile epileptic encephalopathy (Ohtahara syndrome) are discussed in Chapter 586.4. • Miscellaneous Conditions • Miscellaneous conditions include benign neonatal sleep myoclonus and hyperekplexia, which are nonepileptic conditions
