الرحيم الرحمن الله الرحيم بسم الرحمن الله بسم

MECONIUM DISEASEMECONIUM DISEASE

By:By:Dr. zaidoon moayad AltaeeDr. zaidoon moayad Altaee

Mosul Pediatric surgery centerMosul Pediatric surgery center

intestinal obstructionintestinal obstruction in the neonate is one of the most common in the neonate is one of the most common

diagnoses requiring admission to the neonatal diagnoses requiring admission to the neonatal intensive care unit, accounting for as many as intensive care unit, accounting for as many as one third of all admissions.one third of all admissions.

Failure to pass meconium within the first 24 to Failure to pass meconium within the first 24 to 48 hours of life, feeding intolerance, abdominal 48 hours of life, feeding intolerance, abdominal distention, and bilious emesis are hallmarks of distention, and bilious emesis are hallmarks of intestinal obstruction in the newborn period and intestinal obstruction in the newborn period and evoke a differential diagnosis of obstruction evoke a differential diagnosis of obstruction based on anatomic, metabolic, and functional based on anatomic, metabolic, and functional considerations. Strictly speaking, the term considerations. Strictly speaking, the term meconium disease meconium disease refers to meconium ileus refers to meconium ileus and meconium plug syndrome. and meconium plug syndrome.

MECONIUM ILEUSMECONIUM ILEUS Meconium ileusMeconium ileus is one of the most common causes is one of the most common causes

of intestinal obstruction in the newborn, of intestinal obstruction in the newborn, accounting foraccounting for

9% to 33% of neonatal intestinal obstructions.9% to 33% of neonatal intestinal obstructions. It is characterized by extremely viscid, protein-rich, It is characterized by extremely viscid, protein-rich,

inspissated meconium causing an intraluminal inspissated meconium causing an intraluminal obturator typeobturator type

obstruction of the distal ileum. obstruction of the distal ileum. It is the earliest clinical manifestation of cystic fibrosis It is the earliest clinical manifestation of cystic fibrosis

(CF), occurring in approximately 16% of patients (CF), occurring in approximately 16% of patients with that disease.with that disease.

Although meconium ileus may occur with rare Although meconium ileus may occur with rare conditionsconditions

such as pancreatic aplasia and total colonic such as pancreatic aplasia and total colonic aganglionosisaganglionosis

Due to abnormalities of exocrine mucus secretion and Due to abnormalities of exocrine mucus secretion and pancreatic enzyme deficiency, the meconium inpancreatic enzyme deficiency, the meconium in

meconium ileus differs from normal meconium in meconium ileus differs from normal meconium in that:that:

► it has less water contentit has less water content► lower sucrase and lactase levelslower sucrase and lactase levels► increased albumin,increased albumin,► decreased pancreatic enzymesdecreased pancreatic enzymes► concentrations of sodium, potassium, magnesium,concentrations of sodium, potassium, magnesium,► And heavy metals in meconium are reduced in CF And heavy metals in meconium are reduced in CF

patients.patients.

Cystic FibrosisCystic Fibrosis is the most common potentially lethal genetic defect is the most common potentially lethal genetic defect

affecting whites, with approximately 1200 infants with affecting whites, with approximately 1200 infants with CF born each year. CF born each year.

Approximately 30,000 children and young adults live Approximately 30,000 children and young adults live with CF in the United States. It is an inherited with CF in the United States. It is an inherited autosomal recessive disease with a 4% to 5% carrier autosomal recessive disease with a 4% to 5% carrier rate and occurs in 1:3000 torate and occurs in 1:3000 to

1:2000 live births yearly.1:2000 live births yearly. The incidences of CF in non white populations are 1 in The incidences of CF in non white populations are 1 in

15,000 Africo-American births (much lower in native 15,000 Africo-American births (much lower in native Africans), 1 in 31,000 in Asian-American births, 1 in Africans), 1 in 31,000 in Asian-American births, 1 in 10,500 Native American10,500 Native American

Aleut (Eskimo) births, and 1:13,500 in Hispanic-white Aleut (Eskimo) births, and 1:13,500 in Hispanic-white births.births.

Gastrointestinal PathophysiologyGastrointestinal Pathophysiology

Cystic fibrosis is characterized by mucoviscidosis of Cystic fibrosis is characterized by mucoviscidosis of exocrine secretions throughout the body resultingexocrine secretions throughout the body resulting

from abnormal transport of chloride ions across thefrom abnormal transport of chloride ions across the apical membranes of epithelial cells.apical membranes of epithelial cells. The clinical result is chronic obstruction and infection of The clinical result is chronic obstruction and infection of

thethe respiratory tract, insufficiency of the exocrine pancreas,respiratory tract, insufficiency of the exocrine pancreas, and elevated sweat chloride levels.and elevated sweat chloride levels. Other variants can have minimal other manifestations, Other variants can have minimal other manifestations,

suchsuch as patients with chronic sinusitis or men with congenitalas patients with chronic sinusitis or men with congenital bilateral absence of the vas deferens.bilateral absence of the vas deferens.

Abnormal intestinal motility may also contribute to Abnormal intestinal motility may also contribute to the development of meconium ileus.the development of meconium ileus.

Some patients with CF have prolonged small Some patients with CF have prolonged small intestinal transit times. intestinal transit times.

Non-CF diseases associated with abnormal gut Non-CF diseases associated with abnormal gut motility, such as Hirschsprung’s disease and motility, such as Hirschsprung’s disease and chronic intestinal pseudo-obstruction, have been chronic intestinal pseudo-obstruction, have been associated with meconium ileus-like disease, associated with meconium ileus-like disease, signifying that decreased peristalsis may allow for signifying that decreased peristalsis may allow for increased reabsorption of water and the increased reabsorption of water and the development of abnormal meconium.development of abnormal meconium.

Prenatal Diagnosis and Prenatal Diagnosis and ScreeningScreening

The antenatal diagnosis of meconium ileus can be made inThe antenatal diagnosis of meconium ileus can be made in two different groups, a high-risk group and a low-risk two different groups, a high-risk group and a low-risk

group. group. In the low-risk group the diagnosis is suspected when the In the low-risk group the diagnosis is suspected when the

sonographic appearances of meconium ileus are found on sonographic appearances of meconium ileus are found on routine prenatal ultrasonography when there is no routine prenatal ultrasonography when there is no previous family history of CF.previous family history of CF.

All pregnancies subsequent to the birth of a CF affected All pregnancies subsequent to the birth of a CF affected child are considered high risk, and parents of a child with child are considered high risk, and parents of a child with CF are considered to be obligate carriers of a CF mutation.CF are considered to be obligate carriers of a CF mutation.

Pediatric surgeons are often asked to provide prenatal Pediatric surgeons are often asked to provide prenatal consultations to parents of fetuses suspected ofconsultations to parents of fetuses suspected of

bowel obstruction. Meconium ileus must be consideredbowel obstruction. Meconium ileus must be considered in the differential diagnosis, particularly in the high riskin the differential diagnosis, particularly in the high risk fetus.fetus.

Ultrasound EvaluationUltrasound Evaluation Sonographic characteristics associated with Sonographic characteristics associated with

meconium ileus include a hyper echoic, meconium ileus include a hyper echoic, intra-abdominal mass (inspissated intra-abdominal mass (inspissated meconium) dilated bowel and non meconium) dilated bowel and non visualization of the gallbladder. Normal fetal visualization of the gallbladder. Normal fetal meconium, when visualized in the second meconium, when visualized in the second and third trimesters, is usually hypo echoic and third trimesters, is usually hypo echoic or iso echoic to adjacent abdominal or iso echoic to adjacent abdominal structures.structures.

The sensitivity of intra-abdominal echogenic The sensitivity of intra-abdominal echogenic masses in the detection of meconium ileus is masses in the detection of meconium ileus is reported to be between 30% and 70%.reported to be between 30% and 70%.

Clinical PresentationClinical Presentation Meconium ileusMeconium ileus is categorized as either simple is categorized as either simple

or complicated.or complicated. Thickened meconium begins to form in utero.Thickened meconium begins to form in utero. As it obstructs the mid-ileum, proximal small As it obstructs the mid-ileum, proximal small

bowelbowel dilatation and bowel wall thickening occur. dilatation and bowel wall thickening occur.

Approximately one half of these neonates present Approximately one half of these neonates present with a simple uncomplicated obstruction.with a simple uncomplicated obstruction.

The remaining patients present with The remaining patients present with complications of meconium ileus, including complications of meconium ileus, including volvulus, gangrene, atresia, and perforation, volvulus, gangrene, atresia, and perforation, which may result in meconium peritonitis and which may result in meconium peritonitis and giant cystic meconium peritonitis.giant cystic meconium peritonitis.

Simple Meconium IleusSimple Meconium Ileus In simple meconium ileus, the terminal ileum is filled with In simple meconium ileus, the terminal ileum is filled with

firm concretions, is small in diameter, and molds around firm concretions, is small in diameter, and molds around the inspissated lumps of meconium.the inspissated lumps of meconium.

Proximally, the ileum becomes dilated and filled with thick Proximally, the ileum becomes dilated and filled with thick sticky meconium with gas and fluid found within the sticky meconium with gas and fluid found within the small bowel proximal to this area.small bowel proximal to this area.

Newborns with uncomplicated meconium ileus can appear Newborns with uncomplicated meconium ileus can appear healthy immediately after birth.healthy immediately after birth.

However, within 1 to 2 days, they develop abdominal However, within 1 to 2 days, they develop abdominal distention and bilious vomiting, Normal meconium will not distention and bilious vomiting, Normal meconium will not be passed. be passed.

Dilated loops of bowel become visible on examination and Dilated loops of bowel become visible on examination and have a “doughy” character that indents on palpation.have a “doughy” character that indents on palpation.

The rectum and anus are often narrow, a finding that may The rectum and anus are often narrow, a finding that may be misinterpreted as anal stenosis. The presentation of the be misinterpreted as anal stenosis. The presentation of the patient with meconium ileus is similar to that of many patient with meconium ileus is similar to that of many types of neonatal small bowel obstructions. Therefore, the types of neonatal small bowel obstructions. Therefore, the clinician should simultaneously consider and evaluate for clinician should simultaneously consider and evaluate for malrotation, small intestinal atresia, colonic atresia, and malrotation, small intestinal atresia, colonic atresia, and meconium plug syndrome.meconium plug syndrome.

Complicated Meconium IleusComplicated Meconium IleusComplicated meconium ileus may present dramaticallyComplicated meconium ileus may present dramaticallyand immediately after birth. In others, symptomsand immediately after birth. In others, symptomswill develop within 24 hours of birth. Signs of peritonitiswill develop within 24 hours of birth. Signs of peritonitis(abdominal distention, tenderness, abdominal(abdominal distention, tenderness, abdominalwall erythema) as well as clinical evidence of sepsis,wall erythema) as well as clinical evidence of sepsis,may be present on the initial neonatal examinationmay be present on the initial neonatal examinationas a result of in utero perforation or bowel compromise.as a result of in utero perforation or bowel compromise.Abdominal distention can be so severe as toAbdominal distention can be so severe as tocause immediate respiratory distress. A palpable masscause immediate respiratory distress. A palpable masssuggests pseudo cyst formation, which results from in suggests pseudo cyst formation, which results from in

uterouterobowel perforation. Often the neonate is in extremis and bowel perforation. Often the neonate is in extremis and needs urgent resuscitation and surgicalneeds urgent resuscitation and surgicalexploration.exploration.

Radiographic FeaturesRadiographic Features Uncomplicated meconiumUncomplicated meconium ileus is characterized by ileus is characterized by

apatternapattern of unevenly dilated loops of bowel with the variable of unevenly dilated loops of bowel with the variable

presencepresence of air-fluid levels on abdominal radiography.of air-fluid levels on abdominal radiography. The absence of air-fluid levels is due to the increased The absence of air-fluid levels is due to the increased

viscosity of the meconium not allowing an air interface viscosity of the meconium not allowing an air interface with the fluid.with the fluid.

As swallowed air mixes with the tenacious meconium, As swallowed air mixes with the tenacious meconium, bubbles of gas develop.bubbles of gas develop.

This ground-glass appearance depends on the viscosity This ground-glass appearance depends on the viscosity of the meconium and is not a constant feature. Although of the meconium and is not a constant feature. Although each of these features alone is not diagnostic of each of these features alone is not diagnostic of meconium ileus, collectively with a family history of CF, meconium ileus, collectively with a family history of CF, they strongly suggest the diagnosis. Radiographic they strongly suggest the diagnosis. Radiographic findings.findings.

in in complicated meconiumcomplicated meconium ileus vary with the ileus vary with the complication.complication.

Figure. This abdominal Figure. This abdominal radiograph in a neonate radiograph in a neonate

with meconiumwith meconiumileus shows the typical ileus shows the typical

ground-glass ground-glass appearance in theappearance in the

right lower abdomen. Also right lower abdomen. Also note the different-sized note the different-sized loops of distended small loops of distended small

bowel.bowel.

Figure . Classic Figure . Classic radiographic findings radiographic findings

of meconium ileusof meconium ileusare seen on this are seen on this retrograde contrast retrograde contrast

study. First, a “micro study. First, a “micro colon ofcolon of

disuse” is seen. The colon disuse” is seen. The colon is extremely small and is extremely small and

unused. Second,unused. Second,inspissated pellets (filling inspissated pellets (filling

defects) of meconium defects) of meconium are seen in theare seen in the

more proximal small more proximal small bowel. Third, note bowel. Third, note

there is a small bowelthere is a small bowelobstruction as the obstruction as the contrast material has contrast material has

not reached the not reached the markedlymarkedly

dilated loops of small dilated loops of small bowel.bowel.

Diagnostic TestingDiagnostic Testing The diagnosis of CF is established with a sweat testThe diagnosis of CF is established with a sweat test at several weeks of life.at several weeks of life. A concentration of 60 mmol/L in 100 mg of sweat is A concentration of 60 mmol/L in 100 mg of sweat is

diagnostic of CF with 40 to 60 mmol/L being diagnostic of CF with 40 to 60 mmol/L being intermediateintermediate

(but more likely to be diagnostic in infants) and less (but more likely to be diagnostic in infants) and less than than

40 mmol/L being normal.40 mmol/L being normal. To ensure an adequate sweat sample, the test is To ensure an adequate sweat sample, the test is

typically performed at several weeks of life.typically performed at several weeks of life. Neonatal CF screening programs using the Guthrie Neonatal CF screening programs using the Guthrie

bloodblood spot test for raised concentrations of immune reactivespot test for raised concentrations of immune reactive trypsinogen are available in many countries but musttrypsinogen are available in many countries but must be confirmed in a two-stage approach incorporatingbe confirmed in a two-stage approach incorporating CFTR CFTR mutation analysis.mutation analysis.

TreatmentTreatmentNon operative Management of Simple Meconium Non operative Management of Simple Meconium

IleusIleusTreatment of meconium ileus has evolved over theTreatment of meconium ileus has evolved over thepast 55 years. Neonates should initially be managedpast 55 years. Neonates should initially be managedas having a newborn intestinal obstruction. Volumeas having a newborn intestinal obstruction. Volumeresuscitation, gastric decompression, and mechanicalresuscitation, gastric decompression, and mechanicalrespiratory support should be provided as necessary.respiratory support should be provided as necessary.Correction of any coagulation disorders and empiricalCorrection of any coagulation disorders and empiricalbroad-spectrum antibiotic coverage complete this initialbroad-spectrum antibiotic coverage complete this initialmanagement. When meconium ileus is suspectedmanagement. When meconium ileus is suspectedor diagnosed, a diagnostic enema or hyperosmolaror diagnosed, a diagnostic enema or hyperosmolarenema is performed initially to exclude other causesenema is performed initially to exclude other causesof neonatal intestinal obstruction. Many newbornsof neonatal intestinal obstruction. Many newbornswith meconium ileus can be managed non operativelywith meconium ileus can be managed non operativelywith hyperosmolar enema washouts.with hyperosmolar enema washouts.

Operative ManagementOperative Management Simple Meconium IleusSimple Meconium Ileus The indications for operative management of simple The indications for operative management of simple

meconium ileus are inadequate meconium meconium ileus are inadequate meconium evacuation or a complication of the contrast enema evacuation or a complication of the contrast enema (e.g. perforation). (e.g. perforation).

Failure of non operative treatment with hyperosmolar Failure of non operative treatment with hyperosmolar enemas may result from the technical inability to enemas may result from the technical inability to advance the enema column for a sufficient distance advance the enema column for a sufficient distance into the ileum or from an unsuspected, associated into the ileum or from an unsuspected, associated intestinal atresia. If the enema fails to promote intestinal atresia. If the enema fails to promote passage of meconium within 24 to 48 hours, or two passage of meconium within 24 to 48 hours, or two attempts at washout are unsuccessful, an operative attempts at washout are unsuccessful, an operative approach is indicated.approach is indicated.

Figure. At Figure. At operation, operation,

the the meconium in meconium in

a neonate a neonate withwith

cystic cystic fibrosis is fibrosis is very thick very thick

and and tenacious.tenacious.

Complicated Meconium IleusComplicated Meconium Ileus An operation is almost always indicated in An operation is almost always indicated in

cases of complicated meconium ileus. cases of complicated meconium ileus. One exception is a rare in-utero One exception is a rare in-utero

spontaneously sealed perforation with intact spontaneously sealed perforation with intact intestinal continuity and extra-luminal intra- intestinal continuity and extra-luminal intra- peritoneal calcified meconium.peritoneal calcified meconium.

Surgical management includes early Surgical management includes early diagnosis, debridement of necrotic material, diagnosis, debridement of necrotic material, pseudo cyst resection, diverting stoma (s), pseudo cyst resection, diverting stoma (s),

antibiotics, and meticulous postoperative antibiotics, and meticulous postoperative care. Creation of an ostomy is the fastest care. Creation of an ostomy is the fastest and safest course, alleviating concern over and safest course, alleviating concern over bowel discrepancy, anastomotic breakdown, bowel discrepancy, anastomotic breakdown, and return of bowel activity. Decortications and return of bowel activity. Decortications of the cyst wall is recommended, if possible.of the cyst wall is recommended, if possible.

Postoperative ManagementPostoperative Management

The initial postoperative management involves The initial postoperative management involves ongoing resuscitation. Maintenance fluids and ongoing resuscitation. Maintenance fluids and replacement of insensible fluid losses, as well as replacement of insensible fluid losses, as well as gastrointestinal losses (nasogastric suction and gastrointestinal losses (nasogastric suction and ileostomy) must be carefully monitored.ileostomy) must be carefully monitored.

Instillation of 2% or 4% Instillation of 2% or 4% NN- acetylcysteine via a - acetylcysteine via a nasogastric tube or ileostomy will help solubilize nasogastric tube or ileostomy will help solubilize residual meconium. residual meconium.

In the patient with fetal or neonatal bowel In the patient with fetal or neonatal bowel obstruction, CF must be suspected, and obstruction, CF must be suspected, and diagnostic tests should be performed as soon as diagnostic tests should be performed as soon as possible. Stomas placed in the course of surgical possible. Stomas placed in the course of surgical management should be closed as soon as management should be closed as soon as possible (4 to 6 weeks) to help avoid prolonged possible (4 to 6 weeks) to help avoid prolonged problems with fluid, electrolyte, nutritional losses, problems with fluid, electrolyte, nutritional losses, and cholestatic jaundice.and cholestatic jaundice.

PrognosisPrognosis

Improved survival in infants with meconium Improved survival in infants with meconium ileus can be attributed to many factors. ileus can be attributed to many factors. Because of advances in prenatal diagnosis, Because of advances in prenatal diagnosis, pulmonary and neonatal intensive care, pulmonary and neonatal intensive care, nutrition, antibiotics, anesthesia, operative nutrition, antibiotics, anesthesia, operative management, and an improved understanding management, and an improved understanding of the pathophysiology and treatment of the of the pathophysiology and treatment of the complications of CF, the prognosis for infants complications of CF, the prognosis for infants with both complicated and simple meconium with both complicated and simple meconium ileus has improved dramatically. Survival ileus has improved dramatically. Survival rates of 85% to 100% have been reported in rates of 85% to 100% have been reported in uncomplicated meconium ileus and up to 93% uncomplicated meconium ileus and up to 93% in complicated cases.in complicated cases.

MECONIUM PLUG SYNDROMEMECONIUM PLUG SYNDROME

Meconium plug syndrome, a cause of newborn colonicMeconium plug syndrome, a cause of newborn colonic obstruction, was first described in 1956.It was obstruction, was first described in 1956.It was

hypothesized that either colonic motility or the hypothesized that either colonic motility or the character of the meconium was altered, thereby character of the meconium was altered, thereby preventing normal passage and decompression of the preventing normal passage and decompression of the colon in the newborn period.colon in the newborn period.

Under normal conditions, the terminal 2 cm of neonatal Under normal conditions, the terminal 2 cm of neonatal meconium is firm in texture, forming a whitish cap.meconium is firm in texture, forming a whitish cap.

Most newborns pass this cap of meconium before, Most newborns pass this cap of meconium before, during, or shortly after delivery.during, or shortly after delivery.

One in 500 newborns will have a longer, more tenaciousOne in 500 newborns will have a longer, more tenacious obstructive plug. Failure to pass this plug resultsobstructive plug. Failure to pass this plug results in meconium plug syndrome and the term in meconium plug syndrome and the term plugged-upplugged-up babies babies was coinedwas coined

The presentation of meconium plug syndrome isThe presentation of meconium plug syndrome issimilar to that of meconium ileus. Signs include failuresimilar to that of meconium ileus. Signs include failureto pass meconium, bilious vomiting, and abdominalto pass meconium, bilious vomiting, and abdominaldistention with an obstructive pattern on plaindistention with an obstructive pattern on plainabdominal radiographs. Often, the meconium plugabdominal radiographs. Often, the meconium plugmay become dislodged after digital stimulation of themay become dislodged after digital stimulation of theanus and rectum. Fortunately, colon function is anus and rectum. Fortunately, colon function is

generallygenerallypreserved and returns to normal after passage ofpreserved and returns to normal after passage ofthe plug. Ultimately, most of these infants are foundthe plug. Ultimately, most of these infants are foundto be healthy.to be healthy.

Pathologic causes of meconium plug syndrome Pathologic causes of meconium plug syndrome include:include:

CF, small left colon syndrome, and Hirschsprung’sCF, small left colon syndrome, and Hirschsprung’sdisease.Less common causes include congenitaldisease.Less common causes include congenitalhypothyroidism, maternal narcotic addiction, andhypothyroidism, maternal narcotic addiction, andneuronal intestinal dysplasia. Affected newborns shouldneuronal intestinal dysplasia. Affected newborns shouldundergo contrast enemas, which may be therapeutic asundergo contrast enemas, which may be therapeutic aswell as diagnostic. After resolution, a sweat test should bewell as diagnostic. After resolution, a sweat test should beperformed to evaluate for CF and a thyroid-stimulatingperformed to evaluate for CF and a thyroid-stimulatinghormone level should be checked. All patients withhormone level should be checked. All patients withslow passage of meconium require close observationslow passage of meconium require close observationof their stool pattern. Historically, a rectal biopsy hasof their stool pattern. Historically, a rectal biopsy hasbeen recommended to rule out Hirschsprung’s diseasebeen recommended to rule out Hirschsprung’s disease

A recent report documents a 13% incidenceA recent report documents a 13% incidenceof Hirschsprung’s disease in a neonate with of Hirschsprung’s disease in a neonate with

meconiummeconiumplug syndrome. Therefore, a suction biopsy could beplug syndrome. Therefore, a suction biopsy could bereserved for those neonates with an abnormal reserved for those neonates with an abnormal

stoolingstoolingpatternpattern

COMPLICATIONS OF MECONIUMCOMPLICATIONS OF MECONIUMILEUS AND CYSTIC FIBROSISILEUS AND CYSTIC FIBROSIS► Gastroesophageal Reflux DiseaseGastroesophageal Reflux Disease► Biliary Tract DiseaseBiliary Tract Disease► Distal Intestinal Obstruction SyndromeDistal Intestinal Obstruction Syndrome► AppendicitisAppendicitis► IntussusceptionIntussusception► Fibrosing ColonopathyFibrosing Colonopathy